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array:23 [ "pii" => "S1576988723001012" "issn" => "15769887" "doi" => "10.1016/j.vacun.2023.10.006" "estado" => "S300" "fechaPublicacion" => "2024-01-01" "aid" => "331" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2023" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Vacunas. 2024;25:88-96" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S1576988723001000" "issn" => "15769887" "doi" => "10.1016/j.vacun.2023.10.005" "estado" => "S300" "fechaPublicacion" => "2024-01-01" "aid" => "330" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Vacunas. 2024;25:97-108" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Recent advancements in cancer vaccines: A systematic review" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "97" "paginaFinal" => "108" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Avances recientes en vacunas contra el cáncer: una revisión sistemática" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1002 "Ancho" => 1890 "Tamanyo" => 135810 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">The innate immune system controls antigen presentation, which represents both CD4<span class="elsevierStyleHsp" style=""></span>+ as well as CD8<span class="elsevierStyleHsp" style=""></span>+ epitopes activated through activation, and this prevents the growth of tumor tissue.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Stuti Srivastava, Devendra Singh, Sunil Kumar Verma, Minakshi Pandey, Avinash Sharma, Himanshu Pandey, Anshu Mishra" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Stuti" "apellidos" => "Srivastava" ] 1 => array:2 [ "nombre" => "Devendra" "apellidos" => "Singh" ] 2 => array:2 [ "nombre" => "Sunil Kumar" "apellidos" => "Verma" ] 3 => array:2 [ "nombre" => "Minakshi" "apellidos" => "Pandey" ] 4 => array:2 [ "nombre" => "Avinash" "apellidos" => "Sharma" ] 5 => array:2 [ "nombre" => "Himanshu" "apellidos" => "Pandey" ] 6 => array:2 [ "nombre" => "Anshu" "apellidos" => "Mishra" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1576988723001000?idApp=UINPBA00004N" "url" => "/15769887/0000002500000001/v1_202402130601/S1576988723001000/v1_202402130601/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1576988724000013" "issn" => "15769887" "doi" => "10.1016/j.vacun.2023.12.004" "estado" => "S300" "fechaPublicacion" => "2024-01-01" "aid" => "337" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Vacunas. 2024;25:78-87" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Variantes genéticas rs1800629 en <span class="elsevierStyleItalic">TNF</span> y rs2228145 en <span class="elsevierStyleItalic">IL6R</span>: asociación con eventos supuestamente atribuibles a la vacunación e inmunización (ESAVI) y anticuerpos neutralizantes contra SARS-CoV-2 en la población del occidente de México vacunada con AZD1222" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "78" "paginaFinal" => "87" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Genetic variants rs1800629 in <span class="elsevierStyleItalic">TNF</span> and rs2228145 in <span class="elsevierStyleItalic">IL6R:</span> Association with adverse event following immunization (AEFI) and SARS-CoV-2 neutralizing antibodies in western Mexico population that received AZD1222 vaccine" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2776 "Ancho" => 1969 "Tamanyo" => 194585 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Figura " "rol" => "short" ] ] "descripcion" => array:1 [ "es" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">a) Porcentajes de neutralización contra la proteína espiga del SARS-CoV-2 con respecto al sexo; prueba U de Mann-Whitney. b) Porcentajes de neutralización contra la proteína S del SARS-CoV-2 con respecto a los genotipos de la variante rs1800629; prueba U de Mann-Whitney. c) Porcentajes de neutralización contra la proteína S del SARS-CoV-2 con respecto a los genotipos de la variante rs2228145; prueba Kruskal-Wallis. Las líneas horizontales representan mediana y rango intercuartil (P25%-P75%).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Axel Jair Villa-Panduro, Narda M. Corona-Reynaga, Dennis A. Meza-Peña, Mayra Alejandra Enciso Ramírez, Astrid Selene Espinoza García, Jorge Galindo-García, Berenice Sanchez-Caballero, Elia Herminia Valdés-Miramontes, José Francisco Muñoz-Valle, Zyanya Reyes-Castillo" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Axel Jair" "apellidos" => "Villa-Panduro" ] 1 => array:2 [ "nombre" => "Narda M." "apellidos" => "Corona-Reynaga" ] 2 => array:2 [ "nombre" => "Dennis A." "apellidos" => "Meza-Peña" ] 3 => array:2 [ "nombre" => "Mayra Alejandra" "apellidos" => "Enciso Ramírez" ] 4 => array:2 [ "nombre" => "Astrid Selene" "apellidos" => "Espinoza García" ] 5 => array:2 [ "nombre" => "Jorge" "apellidos" => "Galindo-García" ] 6 => array:2 [ "nombre" => "Berenice" "apellidos" => "Sanchez-Caballero" ] 7 => array:2 [ "nombre" => "Elia Herminia" "apellidos" => "Valdés-Miramontes" ] 8 => array:2 [ "nombre" => "José Francisco" "apellidos" => "Muñoz-Valle" ] 9 => array:2 [ "nombre" => "Zyanya" "apellidos" => "Reyes-Castillo" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2445146024000207" "doi" => "10.1016/j.vacune.2024.02.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2445146024000207?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1576988724000013?idApp=UINPBA00004N" "url" => "/15769887/0000002500000001/v1_202402130601/S1576988724000013/v1_202402130601/es/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review Article</span>" "titulo" => "mRNA vaccines in gastric cancer: How close are we?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "88" "paginaFinal" => "96" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "José Dario Portillo-Miño, David Bettin-Gonzalez, Franco Andrés Montenegro Coral" "autores" => array:3 [ 0 => array:4 [ "nombre" => "José Dario" "apellidos" => "Portillo-Miño" "email" => array:1 [ 0 => "cic.investigaciones@hospitalsanpedro.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cr0005" ] ] ] 1 => array:3 [ "nombre" => "David" "apellidos" => "Bettin-Gonzalez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "af0010" ] ] ] 2 => array:3 [ "nombre" => "Franco Andrés Montenegro" "apellidos" => "Coral" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "af0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Grupo de Investigación en Infecciosas y Cáncer (GINFYCA), Fundación Hospital San Pedro, Pasto, Colombia" "etiqueta" => "a" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Faculty of Sciences, Master`s Program in Biological Sciences, Pontificia Universidad Javeriana, Bogotá D.C., Colombia" "etiqueta" => "b" "identificador" => "af0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Centro de Investigaciones Clìnicas, Fundación Hospital San Pedro, Calle 16 Carrera 43, Barrio San Pedro 520003, Pasto, Colombia." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1349 "Ancho" => 2008 "Tamanyo" => 188201 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Mechanism of activation of the immune system for the mRNA vaccine. The mRNA-encoded vaccine allows the expression of surface receptors in the APC (MHC-I, CD80/CD84, and CD70) and activates the CD8+ T cells through the interaction with the TCR, CD28, and CD27. The CD8+ T cells, as soon as they can, search for the tumor cell and bind to its TSA to release the molecules (IL-2, IFN-γ, TNF, etc.) to annihilate the tumor cell. For its part, the APC to activate CD4+ T cells expresses MHC-II, CD80/CD86, CD40, and CD70 on its surface, and interacts with its TCR, CD28, CD40L, and CD27 receptors. The CD4+ T cells activated through the TSA manages to recognize the tumor cell and release the molecules to kill it.</p> <p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Source: The authors.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Gastric cancer (GC) is one of the neoplasms with the highest mortality with around 700 000 deaths in the world, being considered the fifth with the highest number of cases and the third with the highest number of cancer-related deaths.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> Recently, some authors have proposed that by the year 2040, if current rates remain stable, their increase will be 1.8 million new cases and 1.3 million deaths.<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> In this context, GC research has been dizzying in recent years, with the sole purpose of controlling the disease. However, all the effort up to now has not been enough, since chemotherapy, radiotherapy, and conventional surgery have not been sufficiently effective,<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> with overall survival at 5 years of 75% for localized stomach cancer, 35% for regional stomach cancer, and 7% for metastatic stomach cancer.<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> However, in a prediction model during the period 2017–2021 was 42.9% survival rate.<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> In this context, other therapeutic strategies have been developed, such as immunotherapy, which has achieved some benefits. According to the recent NNCN 2022 and ESMO 2022 guidelines, immunotherapy (anti-PD1 and anti-VEGF) makes up the third line of management for advanced GC.<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Despite this, resistance to immunotherapy is challenging in several types of cancer; therefore, the search for new therapeutic options is necessary. Accordingly, the development of a vaccine to control GC would be a promising alternative; either to stimulate an immune response against tumor cells or as a therapeutic option for immunotherapy that allows the restoration of the immune system.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">The COVID-19 pandemic affected millions of people worldwide and economic conditions.<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> The mRNA vaccines for COVID-19 have been one of the most important milestones in the recent history of medicine since they managed to save millions of lives and their development turned out to be relatively fast compared to previous vaccines.<a class="elsevierStyleCrossRefs" href="#bb0045"><span class="elsevierStyleSup">9–12</span></a> The development of mRNA vaccines is a new platform that has been explored in cancer and is an essential alternative to immunotherapy.<a class="elsevierStyleCrossRefs" href="#bb0065"><span class="elsevierStyleSup">13–16</span></a> Cancer immunotherapy is more dependent on monoclonal antibodies, proteins, and cells, as therapeutic targets. The RNA vaccines encode epitopes (tumor-specific antigens [TSA] or tumor-associated antigens [TAA]) that stimulate immune response.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> The cancer immunotherapeutic presents challenges and barriers generating clinical responses relatively low in some patients.<a class="elsevierStyleCrossRefs" href="#bb0085"><span class="elsevierStyleSup">17–19</span></a> In this sense, cancer vaccines are a promising option for cancer treatment. The cancer vaccines are categorized into 4 types: viral vector vaccines, tumor cell immune cell-based, peptide-based, and nucleic acid-based vaccines. The DNA- and RNA-based vaccines have been attempted for benefits in facilitating the delivery of many antigens simultaneously and provoke humoral, and cellular immunity responses that increase the likelihood of tumoral eradication. The peptide-based vaccines and nucleic acid-based vaccines are not restricted by the HLA-specific type. Otherwise, DNA, and RNA vaccines are safe, and well-tolerated.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> In this context, RNA-based vaccines have been used with mRNA.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> The self-replicating (replicon) RNA has been studied recently; consists of replicon replicated RNA stays longer than mRNA inside the target cells (<a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>). Thus, it requires fewer doses of vaccination; 1.25 μg replicon RNA induces the equivalent level of protection compared to 80 μg mRNA.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a></p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0020" class="elsevierStylePara elsevierViewall">This minireview article is intended to present the main approaches to mRNA vaccine for GC and future perspectives.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">General aspects of mRNA vaccines</span><p id="p0025" class="elsevierStylePara elsevierViewall">mRNA vaccines can stimulate the innate and acquired immune response. In this sense, innate immunity, which comprises the initial response to stimulation by a foreign agent for the host, is detected by pathogen-associated molecular patterns (PAMPs), by recognizing the pattern-associated receptors (PRR) of the host. These encompass a wide range of surface receptors for antigens such as Toll-like receptors (TLRs), to act on exogenous substances, mRNA, and formulation components or excipients, such as nanoparticles that can be used as vehicles.<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> Therefore, when the different types of receptors are identified, the innate immune response is triggered through the activation of inflammatory components (cytokines, interleukins), whose main function consists of recruitment, maturation, and attraction to the site of injury of required cells such as NK cells, dendritic cells (DCs), neutrophils, and macrophages.<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> It should be noted that adaptive or memory immunity has a greater and more complex repercussion when faced with a stimulus since it exerts its action in a more specific way. Therefore, to trigger the adaptive response, the target must be exposed so that cells can generate memory.<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a></p><p id="p0030" class="elsevierStylePara elsevierViewall">With the aforementioned, in vaccines, the target would be the mRNA transcribed <span class="elsevierStyleItalic">in vitro</span> transfected in the DC or antigen-presenting cell (APC), which enters the cells by means of endocytosis and is released by endosomal escape to avoid its degradation. Subsequently, the released RNA is captured and translated in the cell's ribosome into the proteins that are going to be encoded to produce the immune and antitumor effects.<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> The proteins that are intended to be generated are TAA and TSA, in such a way that these arise from a process of oncological initiation and progression when the mutated cells express these altered proteins.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> TAA or TSA-expressing cells, which are recognized as endogenous foreign agents and orchestrate the activation of the various signal transduction cascades and cellular trafficking of the immune system.<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">Consequently, the encoded proteins are degraded by the proteasome towards the conversion of peptide units (neoepitopes). Its expression is variable in individuals and is governed by the specific tumor mutational burden of each neoplasia, biological behavior, and excessive concentrations.<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> Thus, APC, DC, B cells, and macrophages identify the neoepitopes that are presented to cytotoxic T-lymphocyte (CTL), CD4<span class="elsevierStyleHsp" style=""></span>+ T cells, and CD8<span class="elsevierStyleHsp" style=""></span>+ T cells through the major histocompatibility complex (MHC), when the protein has already targeted the cytoplasm/endoplasmic reticulum. CD4<span class="elsevierStyleHsp" style=""></span>+ T cells are essential for the activation of CD8<span class="elsevierStyleHsp" style=""></span>+ T cells; and these, in turn, have enormous cytotoxic capacity.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> The most notable mechanisms are the production of IL-2, the upregulation of CD40 ligand (CD40L) and the secretion of cytokines (IFN-γ)<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> (<a class="elsevierStyleCrossRef" href="#f0010">Fig. 2</a>). Immune cells head toward the tumor site and manage to infiltrate the tumor to exert their cytotoxic effect.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0040" class="elsevierStylePara elsevierViewall">In these terms, vaccines can be divided into the following types: (a) cellular vaccines, (b) peptide/protein vaccines, and (c) genetic vaccines (RNA, DNA, and viral).<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> Genetic vaccines aim to introduce genetic material to APCs for the translation of TSA or antigen fragments.<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> mRNA vaccines offer formidable delivery of multiple antigens with a single immunization.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> Another benefit of mRNA vaccines compared to DNA vaccines is that their use would lead to fewer side effects or autoimmune diseases, since they are more quickly degraded, the RNA is also not incorporated into the genome and therefore cannot induce more oncogenic potential.<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">The mRNA stabilization strategies can affect the pharmacokinetics and pharmacodynamics, to permeabilize and optimize the distribution of the biologically active substance. The vehicles must be safe and effective for their formulation, which does not alter the active ingredient but which guarantees delivery strategies of the mRNA appropriately to meet the therapeutic objective.<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a> In this context, the use of lipid and polymeric nanoparticles has performed an efficient mRNA encapsulation process, avoiding its enzymatic degradation by RNAses or exonucleases and allowing an adequate release system.<a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a> This encapsulation method could be explored in the GC, since it has proven to be effective in other types of gastrointestinal cancer, such as colorectal cancer. Cationic lipids can interact with their negative charge with the negative phosphates of mRNA, favoring an encapsulation complex.<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> However, it must be taken into account that an excess of positive charges in this encapsulation process constitutes an additional obstacle; since, these could interact with other positively charged molecules or components of the organism's plasma membrane.<a class="elsevierStyleCrossRef" href="#bb0160"><span class="elsevierStyleSup">32</span></a></p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">The implications of mRNA vaccines in GC</span><p id="p0050" class="elsevierStylePara elsevierViewall">GC is a very heterogeneous disease from a cellular and molecular point of view, with highly variable histogenesis and a very hostile TME. The development of immunotherapy (anti-PD-L1 and CTL4) has allowed generating new approaches about how to use the immune system to attack tumor cells. Based on this, an mRNA vaccine can be considered a new immunotherapeutic tool and could be very promising in the fight against GC. Cancer vaccines must be effective, highly immunogenic, and with innocuous adverse effects, which, unlike prophylactic vaccines for viruses (influenza and pneumococcus), stimulate the immune system when tumor cells are already established.<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a></p><p id="p0055" class="elsevierStylePara elsevierViewall">In other types of vaccines, such as DC or with peptides, they seem to be safe and show an encouraging expectation in the induction of the T cells response in GC.<a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a> Despite the fact that discordant results have been observed in clinical research with a partial and stable immune response; in this sense, in the phase I clinical trial that included 14 patients with advanced and refractory GC, it was safe but with limited clinical efficacy.<a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a> Similarly, a clinical trial with 28 individuals suffering from advanced and refractory GC, in which they combined a DC vaccine with chemotherapy, demonstrated safety, On the other hand, has been shown in the GC, that tumor-infiltrating lymphocytes (TILs) can infiltrate the tumor cells and are considered in the immune response and its clinical significance in the tumoral progression.<a class="elsevierStyleCrossRef" href="#bb0175"><span class="elsevierStyleSup">35</span></a> Another phase I/II, open label, single arm clinical trial and in which they used peptides, had the purpose of evaluating the safety of the OTSGC-A24 vaccine in advanced GC, as an outcome it was well tolerated with a significant response in induction of CTLs.<a class="elsevierStyleCrossRef" href="#bb0180"><span class="elsevierStyleSup">36</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0185"><span class="elsevierStyleSup">37</span></a> In the phase I/II clinical trial in which they evaluated cisplatin and a vaccine with peptides in which the vascular endothelial growth factor receptor 1/2 (VEGFR1/2) was the therapeutic target, of which 12/22 had partial response and 10/22 stable disease with an overall survival of 14.2 months. It should be noted that the induction of CTL was 82% and the therapy was well tolerated.<a class="elsevierStyleCrossRef" href="#bb0190"><span class="elsevierStyleSup">38</span></a></p><p id="p0060" class="elsevierStylePara elsevierViewall">Possible explanations for limited immunogenicity in GC vaccines and LT-based immunotherapy are due to aging of the immune system, late diagnosis in elderly patients, and immune system exhaustion secondary to previous cancer treatments.<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> In addition, it faces the challenges of other types of vaccines such as low immunogenicity, high tumor mutational burden, and immunosuppressive TME,<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> especially, due to the influence of myeloid-derived suppressor cells (MDSCs) on TME, which contributes to decreased efficacy and increased chronic inflammation, which lead to antigenicity.<a class="elsevierStyleCrossRef" href="#bb0195"><span class="elsevierStyleSup">39</span></a> It’s possible that GC immunity continuum characteristics was approximate to “immune excluded” that been defined CD8<span class="elsevierStyleHsp" style=""></span>+ T cells accumulated but have not efficiently infiltrated, transformation growth factor-β (TGF-β), reactive stroma, MDSCs, angiogenesis, and low MHC-I.<a class="elsevierStyleCrossRef" href="#bb0195"><span class="elsevierStyleSup">39</span></a> All these components have been characterized in the TME of GC,<a class="elsevierStyleCrossRef" href="#bb0200"><span class="elsevierStyleSup">40</span></a> and significantly determined prognostic, recurrence, and clinical outcomes.<a class="elsevierStyleCrossRef" href="#bb0205"><span class="elsevierStyleSup">41</span></a> The immune subtypes of gastric adenocarcinoma for mRNA vaccines has been evaluated; in this order of ideas, You et al.,<a class="elsevierStyleCrossRef" href="#bb0210"><span class="elsevierStyleSup">42</span></a> reveals that potential candidates mRNA vaccines as; ADAMTS18, COL10A1, PPEF1, and STRA6.<a class="elsevierStyleCrossRef" href="#bb0210"><span class="elsevierStyleSup">42</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">On the other hand, the bioinformatic analysis has determined the TSA or TAA and immune subtypes of gastric adenocarcinoma; insofar, as the overexpression of antigens such as RAI14, and NREP is associated with poor prognosis, and infiltration of APC.<a class="elsevierStyleCrossRef" href="#bb0215"><span class="elsevierStyleSup">43</span></a> In this study, the immune subtype has a shown molecular, cellular, and clinical characteristic, that allow associated 2 subtypes with survival enhanced, and immune-activated (IS1 and IS2); instead, S13 has been associated with poor prognosis, and the immune subtype without response or “cold type” immune response. In this sense, the authors concluded that GC is a heterogeneous tumor high degree.<a class="elsevierStyleCrossRef" href="#bb0215"><span class="elsevierStyleSup">43</span></a> Some authors suggest that leveraging the antigenicity of “cold tumors” with affordable reagents that consist of are among the few options.<a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a> It is known that neo-epitopes are not solely generated by mutations. In the absence of genome-encoded antigens, the mRNA transcript is sought as a source for immunogenic neo-epitopes.<a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a> It has also been seen that alterations in any of the ribosomal proteins (DRiPs) will yield impaired peptides and enrich the immune-peptidome to be identified for the immune system.<a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0225"><span class="elsevierStyleSup">45</span></a> The viral infection damaging ribosomal proteins will enhance the anti-viral immune response; this approach could be useful in cancer.<a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0230"><span class="elsevierStyleSup">46</span></a> The DRiPs and peptide products of splice-disrupted RNA can be induced in cancer cells; particularly, cancers harboring oncogenic splicing factor mutations, which have partial benefit of immune response of ICI.<a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a> On the other hand, it has been seen that indisulam and sulfonamides affect splicing in tumor cells.<a class="elsevierStyleCrossRef" href="#bb0235"><span class="elsevierStyleSup">47</span></a></p><p id="p0070" class="elsevierStylePara elsevierViewall">It is also difficult to develop cancer vaccines against TAA, since these are self-proteins abnormally expressed by cancer cells. The B- and T cells that recognize these antigens have been eliminated by the immune system as part of central and peripheral tolerance. Thus, targeting TAAs can impair normal cellular expression. This is seen in chimeric antigen receptor engineered T-cell (CAR-T) therapy targeting carcinoembryonic antigen (CEA), leading to severe colitis in colon cancer patients, because the antigen is also normally expressed in the colon normal intestinal tissue.<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0240"><span class="elsevierStyleSup">48</span></a> On the other hand, antigens are immunogenic and cancer-specific; therefore, most are unique to an individual patient's cancer type. This requires personalized therapy, which can be technically complex and requires significant resources and time, further limiting its availability to patients. Many patients with gastrointestinal (GI) malignancies present at an advanced stage and therefore require prompt and effective treatment. Personalized GI cancer vaccines may take too long to develop to adequately treat certain patients.<a class="elsevierStyleCrossRef" href="#bb0245"><span class="elsevierStyleSup">49</span></a> Another potential challenge observed in colorectal cancer and GC is that microsatellite instability (MSI) is very high in some molecular subgroups, which confers broad ligand expression that limits the ability to obtain a complete tumor mutational profile for vaccine development personalized against GI cancer.<a class="elsevierStyleCrossRef" href="#bb0250"><span class="elsevierStyleSup">50</span></a> Tumor sequencing can only reveal mutations in a subset of cancer cells and only at a specific time. Therefore, residual metastatic cells may differ in their mutational status and lead to ineffectiveness of GC vaccines.<a class="elsevierStyleCrossRef" href="#bb0255"><span class="elsevierStyleSup">51</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0260"><span class="elsevierStyleSup">52</span></a> The aforementioned has been considered the cornerstone of the advent of precision oncology that consists of therapeutic decision-making in the function of tumor molecular and genomics characteristics of each patient.<a class="elsevierStyleCrossRefs" href="#bb0265"><span class="elsevierStyleSup">53–55</span></a> Likewise, patients with GI cancers are non-immunologically naïve and have antigen-specific tolerance to cancer. Immune tolerance involves various T cells that are either immunogenic or tolerogenic. Therapeutic vaccines increase both types of T cells and therefore could amplify cells that are involved in both tumor tolerance and rejection, thereby negating therapeutic efficacy.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> Similarly, MDSCs can influence the response to an mRNA vaccine by suppressing TME, since MDSCs have been shown to decrease the efficacy of immunotherapy.<a class="elsevierStyleCrossRef" href="#bb0280"><span class="elsevierStyleSup">56</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0285"><span class="elsevierStyleSup">57</span></a> However, the tumor-infiltrating lymphocyte (TILs) in GC is controversial, but it has been shown can infiltrate the stroma and tumor cells and are considered in the immune response against tumor cells and its clinical significance in the tumoral progression.<a class="elsevierStyleCrossRef" href="#bb0290"><span class="elsevierStyleSup">58</span></a> In this context, the enhanced immune response by RNA vaccines could be useful.<a class="elsevierStyleCrossRef" href="#bb0295"><span class="elsevierStyleSup">59</span></a></p><p id="p0075" class="elsevierStylePara elsevierViewall">Studies using mRNA cancer vaccines have been used to initiate a local immune response in the tumor which then enables immunotherapy to provide a more effective response.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> In this sense, the trials that have currently been carried out in combination with ICI (durvalumab); such as the clinical trial (NTC03164772), in which they showed a better prognosis with a partial or stable response to the disease in non-small cell lung cancer (NSCLC). In the clinical trial (NTC02529072), higher survival rates were obtained when immunotherapy was administered before and after tumor resection, which has suggested that neoadjuvant treatments are a good option in brain tumors (malignant glioma, astrocytoma, and glioblastoma).<a class="elsevierStyleCrossRef" href="#bb0300"><span class="elsevierStyleSup">60</span></a> The clinical trial (NTC00846456) that assessed the efficacy of the mRNA vaccines against a placebo in the tumor stem cells in glioblastoma, in which an increase in survival without disease progression was evidenced.</p><p id="p0080" class="elsevierStylePara elsevierViewall">On the other hand, the use of ICI (anti-CTLA4 and PL-L1) combined with mRNA vaccines is debated, since the progression of the disease has been seen, and this has been attributed to the supersaturation that is generated with the addition of mRNA vaccines and is possibly responsible for the greatest number of adverse events.</p><p id="p0085" class="elsevierStylePara elsevierViewall">A prophylactic vaccine against <span class="elsevierStyleItalic">H. pylori</span> is a therapeutic measure that has been explored with other types of vaccines. In this sense, recombinant vaccines with the virulence factor CagA have been proposed in murine models with the purpose of regulating the balance of the Th1/Th2 response.<a class="elsevierStyleCrossRef" href="#bb0305"><span class="elsevierStyleSup">61</span></a> Regarding peptide vaccines, in one study they immunized with a peptide derived from <span class="elsevierStyleItalic">H. pylori</span> with the amino acid sequence (MVTLINNE), which produced an increase in cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α) and immunoglobulins (IgA and IgG), with a significant increased proliferation of the spleen (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.05). The authors conclude that the MVTLINNE peptide protects mice 100% from <span class="elsevierStyleItalic">H. pylori</span> infection.<a class="elsevierStyleCrossRef" href="#bb0310"><span class="elsevierStyleSup">62</span></a> Otherwise, a DNA vaccine based on the CagW-factor in chitosan nanoparticles has also been evaluated, positioning itself as a promising candidate.<a class="elsevierStyleCrossRef" href="#bb0315"><span class="elsevierStyleSup">63</span></a> An mRNA prophylactic vaccine against <span class="elsevierStyleItalic">H. pylori</span> has not been very well studied and the evidence is scarce. Therefore, exploring this option would be crucial in experimental research and taking it to clinical trials.</p><p id="p0090" class="elsevierStylePara elsevierViewall">The development of clinical trials with mRNA vaccines in GC is scarce. Recently, phase I of the clinical trial of an mRNA vaccine that encodes antigens for advanced GC was presented at the annual meeting of the American Society of Clinical Oncology (ASCO).<a class="elsevierStyleCrossRef" href="#bb0320"><span class="elsevierStyleSup">64</span></a> In this clinical trial (NCT03468244), open-label, randomized, double-blind, and single-arm, the authors reported that it is safe, with no serious adverse effects (neurotoxicity or death), of which erythema, leukopenia, neutropenia, anemia predominated, and thrombocytopenia. In the same way, the immunogenic capacity of the vaccine was considerable, with elevation of IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α, especially IL-8 and IL- 2R reached levels up to 4 times. Another clinical trial (NCT05192460), which evaluates the efficacy and safety of a neoantigen mRNA vaccine in advanced GC, esophageal cancer, and liver cancer, is estimated to end in 2025. The clinical trial (NCT03480152) conducted by Cafri et al.,<a class="elsevierStyleCrossRef" href="#bb0325"><span class="elsevierStyleSup">65</span></a> reveal that this vaccine is safe, and specific T-cell responses against predicted neoepitopes not detected before vaccination. However, the authors do not observe no objective clinical responses in the 4 patients treated in this trial.<a class="elsevierStyleCrossRef" href="#bb0325"><span class="elsevierStyleSup">65</span></a> Furthermore, the selection and detection of vaccine neoantigens are fundamental and immunologic remains a crucial hurdle.<a class="elsevierStyleCrossRef" href="#bb0325"><span class="elsevierStyleSup">65</span></a> The mRNA-based vaccine (mRNA 4650) was clinically evaluated for the digestive system neoplasms, which developed CD4<span class="elsevierStyleHsp" style=""></span>+ and CD8<span class="elsevierStyleHsp" style=""></span>+ T-cell response against tumor neoantigens.<a class="elsevierStyleCrossRef" href="#bb0330"><span class="elsevierStyleSup">66</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0335"><span class="elsevierStyleSup">67</span></a></p><p id="p0095" class="elsevierStylePara elsevierViewall">The summary clinical trials of mRNA vaccines in GC and gastrointestinal tract neoplasms that included GC are shown in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>.</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Future perspectives and new horizons</span><p id="p0100" class="elsevierStylePara elsevierViewall">The success of mRNA vaccines in the fight against severe COVID-19 caused by SARS-CoV-2 has aroused significant interest in their potential application for cancer treatment, particularly in GC. mRNA-based cancer vaccines have shown promise in small trials, and researchers believe that the funding and resources flowing into mRNA vaccine research will also benefit the field of cancer vaccines.<a class="elsevierStyleCrossRef" href="#bb0340"><span class="elsevierStyleSup">68</span></a> Several clinical trials are currently underway to test mRNA treatment vaccines in people with various types of cancer, including pancreatic cancer, colorectal cancer, and melanoma.<a class="elsevierStyleCrossRef" href="#bb0335"><span class="elsevierStyleSup">67</span></a> These have aimed to evaluate the safety and efficacy of mRNA vaccines in the treatment of cancer and may pave the way for more extensive studies in patients with GC.<a class="elsevierStyleCrossRef" href="#bb0340"><span class="elsevierStyleSup">68</span></a></p><p id="p0105" class="elsevierStylePara elsevierViewall">Thus, considering that GC is a highly heterogeneous disease with a hostile TME, making it difficult to develop effective cancer vaccines, researchers need to address issues related to moderate immunogenicity, high tumor mutational burden, and immunosuppressive TME in the development of mRNA vaccines for GC. The GC have a immunophenotype “excluded immune” with an immune response limited.<a class="elsevierStyleCrossRef" href="#bb0195"><span class="elsevierStyleSup">39</span></a> Consequently, strategies to enhance the immune response, such as the infusion and expanded TILs migrate, use of booster with ICIs as an anti-PD1/L1, anti-CTL4, and anti-MDSC can be explored to overcome these challenges.<a class="elsevierStyleCrossRefs" href="#bb0345"><span class="elsevierStyleSup">69–73</span></a> GC tumors often express TAAs that are unique to each patient, which will require personalized therapy, which can be technically complex and time-consuming. While personalized mRNA vaccines have great potential, efforts must be made to optimize RNA stabilization, delivery platforms, and improve clinical efficacy to generate a long-term antitumor response.<a class="elsevierStyleCrossRef" href="#bb0345"><span class="elsevierStyleSup">69</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0370"><span class="elsevierStyleSup">74</span></a> The specific epitopes can be delivered as synthetic peptides can result in useful.<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0375"><span class="elsevierStyleSup">75</span></a></p><p id="p0110" class="elsevierStylePara elsevierViewall">On the other hand, can be useful in the preselection of antigens for enhanced cost-effectively. In this sense, an individual cocktail prepared from an off-the-shelf tumor antigen could be a more cost-efficient approach.<a class="elsevierStyleCrossRef" href="#bb0380"><span class="elsevierStyleSup">76</span></a> The determination of the individual antigen tumor, technologies of sequencing as Oxford NanoporeTM platform is an excellent, and cheaper option.<a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a></p><p id="p0115" class="elsevierStylePara elsevierViewall">It should also be considered that the combination of mRNA vaccines with other treatment modalities, such as ICIs, has shown promise in some clinical trials. Investigation of the optimal combination and sequencing of mRNA vaccines with existing therapies could improve their efficacy in the treatment of GC and other types of cancer.<a class="elsevierStyleCrossRef" href="#bb0340"><span class="elsevierStyleSup">68</span></a> Furthermore, the link between <span class="elsevierStyleItalic">H. pylori</span> infection and GC, the exploration of mRNA vaccines as a prophylactic measure against <span class="elsevierStyleItalic">H. pylori</span> could be crucial to prevent the development of GC. Thus, research on recombinant vaccines and peptides derived from <span class="elsevierStyleItalic">H. pylori</span> antigens can offer valuable information on possible preventive strategies.<a class="elsevierStyleCrossRef" href="#bb0340"><span class="elsevierStyleSup">68</span></a></p><p id="p0120" class="elsevierStylePara elsevierViewall">To combine the RNA vaccines with the fraction of double-stranded (ds) RNA booster or the adjuvant stimulus through NF-κB activation by TLR3 which binds to the dsRNA<a class="elsevierStyleCrossRef" href="#bb0385"><span class="elsevierStyleSup">77</span></a>; or by fraction of the mRNA with protamine, which then acts as an adjuvant that induced an effective immune response through TLR7 signaling.<a class="elsevierStyleCrossRef" href="#bb0390"><span class="elsevierStyleSup">78</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0395"><span class="elsevierStyleSup">79</span></a> This immunization also led to the production of type I interferon, as proinflammatory cytokines and chemokines.<a class="elsevierStyleCrossRef" href="#bb0400"><span class="elsevierStyleSup">80</span></a></p><p id="p0125" class="elsevierStylePara elsevierViewall">The researchers suggest aphorisms that can help overcome the obstacles and barriers to the success of mRNA vaccines, that can be applicable to the development of mRNA vaccine to GC as: (1) tumor sequencing must be fast and cheap to allow tailored individual selection of antigens possibly via panel sequencing devices, (2) RNA vaccines production must be economical, (3) the production of individual mRNA vaccines for the only patient is complex and not be feasible, (4) the RNA vaccine must be formulated to be stable at -20°C to circumvent excessively complex transport and storage, (5) the bureaucracy and excessive expend must be reduced.<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a></p><p id="p0130" class="elsevierStylePara elsevierViewall">Several studies further understanding of the mechanisms of mRNA vaccines to GC are required through research to elucidate the mechanisms by which mRNA vaccines stimulate the immune response against tumor cells, which would allow understanding of how vaccines mRNAs activate immune cells, including CTL, and influencing the TME will be essential to optimize vaccine design and efficacy.<a class="elsevierStyleCrossRef" href="#bb0350"><span class="elsevierStyleSup">70</span></a></p><p id="p0135" class="elsevierStylePara elsevierViewall">Finally, the use of RNA-based treatment of cancer immunotherapy and mRNA vaccines are undoubtedly considered an immunotherapy tool against GC.<a class="elsevierStyleCrossRef" href="#bb0365"><span class="elsevierStyleSup">73</span></a> The development of mRNA vaccines and much of the growing knowledge about new immunotherapy targets in the next 10 years will be rapid and crucial for a greater understanding of the immunology of T cells and to fight cancer.<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> It will likely allow us to get even closer to developing an mRNA vaccine for GC. There is still a long way to go, but current research has shed a lot of light that the mRNA vaccine is a feasible and hopeful option in this ongoing fight to reduce GC mortality.</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Funding source</span><p id="p0140" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres2089107" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1781488" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2089108" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1781487" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "s0010" "titulo" => "General aspects of mRNA vaccines" ] 6 => array:2 [ "identificador" => "s0015" "titulo" => "The implications of mRNA vaccines in GC" ] 7 => array:2 [ "identificador" => "s0020" "titulo" => "Future perspectives and new horizons" ] 8 => array:2 [ "identificador" => "s0025" "titulo" => "Funding source" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-08-15" "fechaAceptado" => "2023-10-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1781488" "palabras" => array:4 [ 0 => "Gastric cancer" 1 => "Immunotherapy" 2 => "Vaccines" 3 => "mRNA" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1781487" "palabras" => array:4 [ 0 => "Cancer gástrico" 1 => "inmunoterapia" 2 => "vacunas" 3 => "ARNm" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Gastric cancer (GC) is one of the neoplasms with higher mortality, causing around 700 000 deaths worldwide. Despite efforts in GC research, chemotherapy, radiotherapy, and conventional surgery have not been sufficiently effective. Immunotherapy has been proposed as an alternative, and the most recent guidelines recommend its use as a third-line treatment for advanced GC. In this context, the development of an mRNA vaccine to control GC is presented as a promising alternative, either to stimulate an immune response against tumor cells or as a therapeutic option to restore the immune system and reduce mortality from GC. Although there is still a long way to go, technological advances and ongoing research bring us closer to the development of an mRNA vaccine for GC that can be administered in combination with immune checkpoint inhibitors.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="as0010" class="elsevierStyleSection elsevierViewall"><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">El cáncer gástrico (CG) es una de las neoplasias con mayor mortalidad, provocando alrededor de 700.000 muertes en todo el mundo. A pesar de los esfuerzos en la investigación de GC, la quimioterapia, la radioterapia y la cirugía convencional no han sido lo suficientemente efectivas. La inmunoterapia se ha propuesto como opción y las guías más recientes recomiendan su uso como tratamiento de tercera línea para el CG avanzado. En este contexto, el desarrollo de una vacuna de ARNm para el control de CG se presenta como una alternativa prometedora, ya sea para estimular una respuesta inmune contra las células tumorales o como una opción terapéutica para restaurar el sistema inmunológico y reducir la mortalidad por CG. Aunque todavía queda mucho camino por recorrer, los avances tecnológicos y la investigación en curso nos acercan al desarrollo de una vacuna de ARNm para CG que pueda administrarse en combinación con inhibidores de puntos de control inmunitarios.</p></span>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1426 "Ancho" => 1772 "Tamanyo" => 151409 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Mechanism of conventional and self-amplification mRNA vaccines. The mRNA with the genes of interest enters the APC through the endosomal route and is released into the cytoplasm so that the proteins of interest are produced in the endoplasmic reticulum, some of which are degraded by the proteasome, resulting in peptides. The peptides that form the major histocompatibility complex (MHC-I) are encapsulated and by exosomal route are located on the surface and subsequently activate CD8+ T cells. Self-amplifying mRNA uses a transporter such as alphaviruses to carry a broader chain of coding genes and release a greater number of mRNAs into the cytoplasm that are translated into proteins. When they are degraded by the proteasome, the peptides released are more numerous, and with their organizational modification in MHC-I, they are encapsulated and move to the surface to be released by the exosomal route.</p> <p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Source: The authors.</p>" ] ] 1 => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1349 "Ancho" => 2008 "Tamanyo" => 188201 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Mechanism of activation of the immune system for the mRNA vaccine. The mRNA-encoded vaccine allows the expression of surface receptors in the APC (MHC-I, CD80/CD84, and CD70) and activates the CD8+ T cells through the interaction with the TCR, CD28, and CD27. The CD8+ T cells, as soon as they can, search for the tumor cell and bind to its TSA to release the molecules (IL-2, IFN-γ, TNF, etc.) to annihilate the tumor cell. For its part, the APC to activate CD4+ T cells expresses MHC-II, CD80/CD86, CD40, and CD70 on its surface, and interacts with its TCR, CD28, CD40L, and CD27 receptors. The CD4+ T cells activated through the TSA manages to recognize the tumor cell and release the molecules to kill it.</p> <p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Source: The authors.</p>" ] ] 2 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Source: The authors.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N° \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tittle \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Phase \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcome \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Identifier \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Patients with Advanced Digestive System Neoplasms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interventional, A single arm, open label, randomized, double-blind, is designed to determinate the safety, tolerability, and effectiveness of personalized mRNA tumor vaccine. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No applicable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 patients (esophageal squamous carcinoma, gastric adenocarcinoma) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT03468244 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Personalized mRNA Vaccine Encoding Neoantigen Alone in Subjects with Advanced Digestive System Neoplasms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interventional, open label, single arm is designed for assess the safety, feasibility, and efficacy of personalized mRNA vaccine. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 patients (subjects with advanced with advanced digestive system neoplasms). \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT06019702 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Personalized mRNA Vaccine Encoding Neoantigen in Combination with Standard First-line Treatment in Subjects with Advanced Digestive System \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interventional, open label, single arm, attempt assess of personalized mRNA vaccine iNeo-Vac-R01 in combination for \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 patients with digestive system neoplasms. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT06026800 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Subjects with Resected Digestive System Neoplasms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interventional, open-label, single arm clinical study, is designed to assess safety, feasibility, and efficacy. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phase I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 patients with resected digestive system neoplasms. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT06026774 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Safety and Efficacy of Personalized Neoantigen Vaccine in Advanced Gastric Cancer, Esophageal Cancer, and Liver Cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interventional, open-label, single arm exploratory study of mRNA antigen tumor vaccine, attempt assess efficacy and tolerability of mRNA neoantigen tumor vaccine with or without PD-1/L1. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not applicable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 patients (advanced gastric cancer, esophageal cancer, and liver cancer). \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NCT05192460 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3458536.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">The clinical trials of mRNA vaccines of GC.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:80 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." 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