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Vaccines
Special Issues
Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives
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Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: 1 May 2026 | Viewed by 12106

Special Issue Editors

Dr. Xingxing He

E-Mail Website
Guest Editor
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
Interests: cancer therapy
Prof. Dr. Honglin Jin

E-Mail Website
Guest Editor
College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China
Interests: research on new technologies and targets for tumor immunotherapy, as well as related immune mechanisms, with a focus on interdisciplinary integration and clinical transformation

Special Issue Information

Dear Colleagues,

In recent years, immunotherapy has gained significant momentum in the field of cancer treatment. Tumor vaccines are a favorable approach to cancer immunotherapy and include mRNA vaccines, DNA vaccines, and others. Eventually, vaccination may become the first truly personalized treatment for cancer. mRNA vaccines have become a promising platform for cancer immunotherapy as SARS-CoV-2 vaccines based on mRNA platforms have been rigorously evaluated and approved for widespread use. However, tumor vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. What is more, the adjuvant mechanisms of triggering antibody responses remain poorly understood. To conclude, there are a variety of problems to address in the area of tumor vaccines.

This Special Issue aims to discuss the latest processes, prevailing challenges, and future perspectives related to the development of tumor vaccines. In this Special Issue, original research articles, case reports, and reviews are welcome. Research areas may include (but are not limited to) the following: basic research and clinical trials on tumor vaccines, the nature of tumor vaccines, vaccine adjuvants, and delivery strategies.

We look forward to receiving your contributions.

Dr. Xingxing He
Prof. Dr. Honglin Jin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor vaccine
  • mRNA vaccine
  • personalized medicine
  • adjuvant
  • delivery strategies
  • cancer immunotherapy
  • personalized vaccines

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Published Papers (5 papers)

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Research

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15 pages, 4481 KiB  
Article
In Situ Tumor Vaccination Using Lipid Nanoparticles to Deliver Interferon-β mRNA Cargo
by Kenji Kimura, Aidan Aicher, Emma Niemeyer, Phurin Areesawangkit, Caitlin Tilsed, Karen P. Fong, Tyler E. Papp, Steven M. Albelda, Hamideh Parhiz and Jarrod D. Predina
Vaccines 2025, 13(2), 178; https://doi.org/10.3390/vaccines13020178 - 13 Feb 2025
Viewed by 1231
Abstract
Background: In situ cancer vaccination is a therapeutic approach that involves stimulating the immune system in order to generate a polyclonal, anti-tumor response against an array of tumor neoantigens. Traditionally, in situ vaccination approaches have utilized adenoviral vectors to deliver immune-stimulating genes directly [...] Read more.
Background: In situ cancer vaccination is a therapeutic approach that involves stimulating the immune system in order to generate a polyclonal, anti-tumor response against an array of tumor neoantigens. Traditionally, in situ vaccination approaches have utilized adenoviral vectors to deliver immune-stimulating genes directly to the tumor microenvironment. Lipid nanoparticle (LNP)-mediated delivery methods offer several advantages over adenoviral delivery approaches, including increased safety, repeated administration potential, and enhanced tumor microenvironment activation. Methods: To explore in situ vaccination using LNPs, we evaluated LNP-mediated delivery of a reporter gene, mCherry, and an immune-stimulating gene, IFNβ, in several in vitro and in vivo models of lung cancer. Results: In vitro experiments demonstrated successful transfection of murine cancer cell lines with LNPs carrying both mCherry and IFN-β mRNA, resulting in high expression levels and IFNβ production. In vivo studies using LLC.ova flank tumors showed that intratumoral injection of IFNβ-mRNA LNPs led to significant IFNβ production within the tumor microenvironment, with minimal systemic exposure. Therapeutic efficacy was evaluated by injecting established LLC.ova flank tumors with IFNβ-mRNA LNPs bi-weekly for two weeks. Treated tumors showed significant growth inhibition compared to controls. Flow cytometric analysis of tumor-infiltrating leukocytes revealed that tumors injected with IFNβ-mRNA LNPs were associated with an increased CD8:CD4 T-cell ratio among lymphocytes, more CD69-expressing CD8 T-cells, and an increased presence of M1 macrophages. Efficacy and an abscopal effect were confirmed in a squamous cell carcinoma model, MOC1. No toxicity was observed. Conclusions: These findings show that intratumoral LNP delivery of immune-stimulating mRNA transcripts, such as IFNβ, can effectively stimulate local anti-tumor immune responses and warrants further investigation as a potential immunotherapeutic approach for cancer. Full article
(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)
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21 pages, 3003 KiB  
Article
Characterization of the Anti-Viral and Vaccine-Specific CD8+ T Cell Composition upon Treatment with the Cancer Vaccine VSV-GP
by Tamara Hofer, Lisa Pipperger, Sarah Danklmaier, Krishna Das and Guido Wollmann
Vaccines 2024, 12(8), 867; https://doi.org/10.3390/vaccines12080867 - 1 Aug 2024
Viewed by 1828
Abstract
Numerous factors influence the magnitude and effector phenotype of vaccine-induced CD8+ T cells, thereby potentially impacting treatment efficacy. Here, we investigate the effect of vaccination dose, route of immunization, presence of a target antigen-expressing tumor, and heterologous prime-boost with peptide vaccine partner [...] Read more.
Numerous factors influence the magnitude and effector phenotype of vaccine-induced CD8+ T cells, thereby potentially impacting treatment efficacy. Here, we investigate the effect of vaccination dose, route of immunization, presence of a target antigen-expressing tumor, and heterologous prime-boost with peptide vaccine partner following vaccination with antigen-armed VSV-GP. Our results indicate that a higher vaccine dose increases antigen-specific CD8+ T cell proportions while altering the phenotype. The intravenous route induces the highest proportion of antigen-specific CD8+ T cells together with the lowest anti-viral response followed by the intraperitoneal, intramuscular, and subcutaneous routes. Moreover, the presence of a B16-OVA tumor serves as pre-prime, thereby increasing OVA-specific CD8+ T cells upon vaccination and thus altering the ratio of anti-tumor versus anti-viral CD8+ T cells. Interestingly, tumor-specific CD8+ T cells exhibit a different phenotype compared to bystander anti-viral CD8+ T cells. Finally, the heterologous combination of peptide and viral vaccine elicits the highest proportion of antigen-specific CD8+ T cells in the tumor and tumor-draining lymph nodes. In summary, we provide a basic immune characterization of various factors that affect anti-viral and vaccine target-specific CD8+ T cell proportions and phenotypes, thereby enhancing our vaccinology knowledge for future vaccine regimen designs. Full article
(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)
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Review

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23 pages, 2295 KiB  
Review
Current Development of Therapeutic Vaccines in Lung Cancer
by Jesus Salvador Flores Banda, Sanjana Gangane, Fatima Raza and Erminia Massarelli
Vaccines 2025, 13(2), 185; https://doi.org/10.3390/vaccines13020185 - 14 Feb 2025
Viewed by 1675
Abstract
Cancer vaccines have a potential to change the current landscape of immunotherapy research and development. They target and neutralize specific tumor cells by utilizing the body’s own immune system which offers a promising modality in treating various cancers including lung cancer. Historically, prior [...] Read more.
Cancer vaccines have a potential to change the current landscape of immunotherapy research and development. They target and neutralize specific tumor cells by utilizing the body’s own immune system which offers a promising modality in treating various cancers including lung cancer. Historically, prior vaccination approaches specifically towards lung cancer have posed several challenges but also potential with early phase I/II trials showing improved overall survival. With better understanding of the body’s immune system as well as advancements in vaccine development, the use of vaccines to target lung cancer cells in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) has shown promise but also challenges in the setting of advanced stage cancers, tumor resistance mechanisms, immune evasion, and tumor heterogeneity. The proposed solution is to enroll patients in the early stages of the disease, rather than waiting until progression occurs. Additionally, future efforts will focus on the targeted identification of specific and novel tumor neo-antigens. This review offers discussion and analysis of both completed and ongoing trials utilizing different strategies for vaccine development in relation to treating lung cancer as well as current challenges faced. Full article
(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)
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39 pages, 2034 KiB  
Review
Tumor Neoepitope-Based Vaccines: A Scoping Review on Current Predictive Computational Strategies
by Luiz Gustavo do Nascimento Rocha, Paul Anderson Souza Guimarães, Maria Gabriela Reis Carvalho and Jeronimo Conceição Ruiz
Vaccines 2024, 12(8), 836; https://doi.org/10.3390/vaccines12080836 - 24 Jul 2024
Viewed by 2206
Abstract
Therapeutic cancer vaccines have been considered in recent decades as important immunotherapeutic strategies capable of leading to tumor regression. In the development of these vaccines, the identification of neoepitopes plays a critical role, and different computational methods have been proposed and employed to [...] Read more.
Therapeutic cancer vaccines have been considered in recent decades as important immunotherapeutic strategies capable of leading to tumor regression. In the development of these vaccines, the identification of neoepitopes plays a critical role, and different computational methods have been proposed and employed to direct and accelerate this process. In this context, this review identified and systematically analyzed the most recent studies published in the literature on the computational prediction of epitopes for the development of therapeutic vaccines, outlining critical steps, along with the associated program’s strengths and limitations. A scoping review was conducted following the PRISMA extension (PRISMA-ScR). Searches were performed in databases (Scopus, PubMed, Web of Science, Science Direct) using the keywords: neoepitope, epitope, vaccine, prediction, algorithm, cancer, and tumor. Forty-nine articles published from 2012 to 2024 were synthesized and analyzed. Most of the identified studies focus on the prediction of epitopes with an affinity for MHC I molecules in solid tumors, such as lung carcinoma. Predicting epitopes with class II MHC affinity has been relatively underexplored. Besides neoepitope prediction from high-throughput sequencing data, additional steps were identified, such as the prioritization of neoepitopes and validation. Mutect2 is the most used tool for variant calling, while NetMHCpan is favored for neoepitope prediction. Artificial/convolutional neural networks are the preferred methods for neoepitope prediction. For prioritizing immunogenic epitopes, the random forest algorithm is the most used for classification. The performance values related to the computational models for the prediction and prioritization of neoepitopes are high; however, a large part of the studies still use microbiome databases for training. The in vitro/in vivo validations of the predicted neoepitopes were verified in 55% of the analyzed studies. Clinical trials that led to successful tumor remission were identified, highlighting that this immunotherapeutic approach can benefit these patients. Integrating high-throughput sequencing, sophisticated bioinformatics tools, and rigorous validation methods through in vitro/in vivo assays as well as clinical trials, the tumor neoepitope-based vaccine approach holds promise for developing personalized therapeutic vaccines that target specific tumor cancers. Full article
(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)
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24 pages, 2059 KiB  
Review
Development and Clinical Applications of Therapeutic Cancer Vaccines with Individualized and Shared Neoantigens
by Qing Hao, Yuhang Long, Yi Yang, Yiqi Deng, Zhenyu Ding, Li Yang, Yang Shu and Heng Xu
Vaccines 2024, 12(7), 717; https://doi.org/10.3390/vaccines12070717 - 27 Jun 2024
Cited by 2 | Viewed by 3941
Abstract
Neoantigens, presented as peptides on the surfaces of cancer cells, have recently been proposed as optimal targets for immunotherapy in clinical practice. The promising outcomes of neoantigen-based cancer vaccines have inspired enthusiasm for their broader clinical applications. However, the individualized tumor-specific antigens (TSA) [...] Read more.
Neoantigens, presented as peptides on the surfaces of cancer cells, have recently been proposed as optimal targets for immunotherapy in clinical practice. The promising outcomes of neoantigen-based cancer vaccines have inspired enthusiasm for their broader clinical applications. However, the individualized tumor-specific antigens (TSA) entail considerable costs and time due to the variable immunogenicity and response rates of these neoantigens-based vaccines, influenced by factors such as neoantigen response, vaccine types, and combination therapy. Given the crucial role of neoantigen efficacy, a number of bioinformatics algorithms and pipelines have been developed to improve the accuracy rate of prediction through considering a series of factors involving in HLA-peptide-TCR complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. On the other hand, shared neoantigens, originating from driver mutations at hot mutation spots (e.g., KRASG12D), offer a promising and ideal target for the development of therapeutic cancer vaccines. A series of clinical practices have established the efficacy of these vaccines in patients with distinct HLA haplotypes. Moreover, increasing evidence demonstrated that a combination of tumor associated antigens (TAAs) and neoantigens can also improve the prognosis, thus expand the repertoire of shared neoantigens for cancer vaccines. In this review, we provide an overview of the complex process involved in identifying personalized neoantigens, their clinical applications, advances in vaccine technology, and explore the therapeutic potential of shared neoantigen strategies. Full article
(This article belongs to the Special Issue Tumor Vaccines: Current Processes, Prevailing Challenges and Future Perspectives)
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