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Vaccines
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Therapeutic Cancer Vaccines: Advances, Challenges, and Future Directions
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Therapeutic Cancer Vaccines: Advances, Challenges, and Future Directions

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

Deadline for manuscript submissions: 31 May 2027 | Viewed by 4478

Editors

Prof. Dr. Erminia Massarelli

E-Mail Website
Guest Editor
Hope Cancer Center, University of Texas at Tyler School of Medicine, Tyler, TX, USA
Interests: lung cancer; immunotherapy; targeted therapy
Prof. Dr. Victoria M. Villaflor

E-Mail Website1 Website2
Guest Editor
1. School of Medicine, UC Irvine, 1001 Health Sciences Road, Irvine, CA 92697, USA
2. Chao Family Comprehensive Cancer Center, UCI Health, 200 S Manchester Ave, Suite 400, Orange, CA 92868, USA
Interests: oncology; hematology; cancer vaccine; cancer immunotherapy

Special Issue Information

Dear Colleagues,

We welcome contributions to our upcoming Special Issue, "Therapeutic Cancer Vaccines: Advances, Challenges, and Future Directions”.

This Special Issue solicits articles that critically analyze the evolving landscape of therapeutic cancer vaccine development, focusing on solid tumors and malignant hematology. This Special Issue will explore recent research initiatives and clinical trials implementing diverse vaccination strategies. By identifying the successes and challenges within this field, this Special Issue aims to enhance our understanding of how cancer vaccines can improve treatment outcomes, whether administered alone or combined with standard of care therapy and/or immunotherapy.

This Special Issue will encompass a comprehensive overview of the current research landscape, highlighting completed and ongoing clinical trials, alongside insights from recognized experts in the field. It will detail various vaccination strategies, analyze the challenges and obstacles encountered, including issues related to efficacy and the specific patient populations that may respond favorably to vaccines, and delineate future directions to overcome these challenges within cancer vaccine development.

We welcome original research articles and review papers. Potential research areas include, but are not limited to, the following topics:

  • Therapeutic vaccines in solid tumors;
  • Therapeutic vaccines in malignant hematology;
  • Immunotherapy and cancer vaccines;
  • Cancer vaccine clinical trials.

We look forward to your valuable contributions.

Prof. Dr. Erminia Massarelli
Prof. Dr. Victoria M. Villaflor
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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • therapeutic cancer vaccines
  • clinical trials
  • solid tumors
  • malignant hematology
  • peptide vaccines
  • DNA vaccines
  • vector vaccines
  • dendritic cell vaccines
  • allogenic vaccines
  • mRNA vaccines

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Published Papers (4 papers)

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Review

26 pages, 10066 KB  
Review
Therapeutic Cancer Vaccines: Mechanisms, Clinical Progress, and Future Directions
by Kendra Wilson, Jesus Salvador Flores Banda, Sanjana Bukkapatnam, Fatima Raza and Erminia Massarelli
Vaccines 2026, 14(7), 599; https://doi.org/10.3390/vaccines14070599 - 7 Jul 2026
Viewed by 259
Abstract
Therapeutic cancer vaccines have emerged as a promising approach in cancer immunotherapy, aiming to stimulate the immune system to recognize and eliminate malignant cells. Despite this potential, clinical efficacy has remained variable across multiple vaccine platforms. This review synthesizes completed clinical trials evaluating [...] Read more.
Therapeutic cancer vaccines have emerged as a promising approach in cancer immunotherapy, aiming to stimulate the immune system to recognize and eliminate malignant cells. Despite this potential, clinical efficacy has remained variable across multiple vaccine platforms. This review synthesizes completed clinical trials evaluating major therapeutic cancer vaccine modalities, including peptide-based, nucleic acid--based, dendritic cell, whole cell, and viral and bacterial vector--based vaccines, with a focus on safety, immunogenicity, and clinical outcomes for diverse tumor types. Overall, these vaccines demonstrate a favorable safety profile; however, clinical efficacy as monotherapy has been limited. Clinical outcomes vary by platform and tumor type and are influenced by factors such as antigen selection, tumor heterogeneity and immunosuppressive tumor microenvironment (TME). Recent advances in antigen design, vaccine technologies, and combination strategies are redefining the role of therapeutic cancer vaccines in oncology. Future progress will depend on optimizing their integration with standard treatment modalities, particularly immune checkpoint inhibitors. Full article
(This article belongs to the Special Issue Therapeutic Cancer Vaccines: Advances, Challenges, and Future Directions)
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19 pages, 2097 KB  
Review
Cancer Vaccines in Genitourinary Malignancies: Current Advances and Future Directions
by Haider Altay, Ibrahim Al-Hashimi, Josh Matthews, Grace DeAlessandro and Ghanshyam H. Ghelani
Vaccines 2026, 14(6), 497; https://doi.org/10.3390/vaccines14060497 - 1 Jun 2026
Viewed by 1024
Abstract
Therapeutic cancer vaccines are a promising immunotherapy approach in genitourinary (GU) cancers, designed to stimulate antitumor immune responses through antigen-specific T-cell activation. Although agents such as bacillus Calmette–Guérin in bladder cancer and sipuleucel-T in prostate cancer have shown success, vaccine monotherapy has generally [...] Read more.
Therapeutic cancer vaccines are a promising immunotherapy approach in genitourinary (GU) cancers, designed to stimulate antitumor immune responses through antigen-specific T-cell activation. Although agents such as bacillus Calmette–Guérin in bladder cancer and sipuleucel-T in prostate cancer have shown success, vaccine monotherapy has generally produced limited clinical benefit due to tumor heterogeneity, poor immune infiltration, and immunosuppressive tumor microenvironments. Multiple vaccine platforms have demonstrated safety and immunogenicity in prostate, renal cell, and urothelial cancers, but efficacy remains modest. Current strategies focus on multi-antigen targeting, improved antigen presentation, and combination therapies with immune checkpoint inhibitors, radiotherapy, and targeted agents to enhance antitumor activity. Advances in personalized vaccine design and delivery systems are driving progress, though challenges such as manufacturing complexity, cost, and biomarker development remain. Ongoing translational and clinical research will be critical to improving the effectiveness of vaccine-based immunotherapy in GU malignancies. Full article
(This article belongs to the Special Issue Therapeutic Cancer Vaccines: Advances, Challenges, and Future Directions)
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30 pages, 779 KB  
Review
Therapeutic Cancer Vaccines in B-Cell Malignancies and Multiple Myeloma
by Vishrut Shah and Joseph Todd Martins
Vaccines 2026, 14(6), 473; https://doi.org/10.3390/vaccines14060473 - 26 May 2026
Viewed by 497
Abstract
Therapeutic cancer vaccines represent a rational immunotherapeutic strategy aimed at inducing tumor-specific adaptive immune responses in patients with established malignancies. In contrast to prophylactic vaccines, these approaches must function within immunosuppressive tumor microenvironments characterized by antigenic heterogeneity, immune dysfunction, and dynamic tumor evolution. [...] Read more.
Therapeutic cancer vaccines represent a rational immunotherapeutic strategy aimed at inducing tumor-specific adaptive immune responses in patients with established malignancies. In contrast to prophylactic vaccines, these approaches must function within immunosuppressive tumor microenvironments characterized by antigenic heterogeneity, immune dysfunction, and dynamic tumor evolution. Effective vaccine design requires the integration of three essential components: the selection of appropriate tumor-associated or tumor-specific antigens, efficient delivery platforms that enable antigen presentation, and adjuvant systems that promote robust T-cell priming and expansion. Initial clinical investigations in B-cell malignancies and multiple myeloma demonstrated that idiotype-based vaccines can elicit tumor-specific immune responses. However, durable clinical benefit has been inconsistent, reflecting limitations in antigen selection, suboptimal immunogenicity, and tumor-mediated immune evasion. Over the past decade, advances in tumor genomics, next-generation sequencing, and immune monitoring have enabled the development of next-generation vaccine platforms, including dendritic cell-based approaches, personalized neoantigen vaccines, and mRNA-based technologies. Emerging evidence suggests that vaccine efficacy is highly dependent on disease context. Biologically favorable settings such as minimal residual disease (MRD) and post-transplant immune reconstitution provide reduced tumor burden and improved immune competence, thereby enhancing the likelihood of effective immune priming. In parallel, combination strategies incorporating immune checkpoint inhibitors, immunomodulatory agents, and cellular therapies are increasingly being explored to overcome tumor-induced immunosuppression. This review synthesizes current knowledge of therapeutic cancer vaccines in B-cell malignancies and multiple myeloma, with emphasis on immunologic mechanisms, antigen selection, vaccine platforms, and clinical evidence. We further propose a conceptual framework integrating tumor biology, immune context, and combination strategies to guide the rational development of next-generation vaccine therapies. Full article
(This article belongs to the Special Issue Therapeutic Cancer Vaccines: Advances, Challenges, and Future Directions)
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20 pages, 1185 KB  
Review
Therapeutic Vaccines for Head and Neck Squamous Cell Carcinoma and Nasopharyngeal Carcinoma
by Michael Baliton, Duha Alfatlawi, Shirin Attarian, Rupali Nabar and Victoria Villaflor
Vaccines 2026, 14(4), 321; https://doi.org/10.3390/vaccines14040321 - 3 Apr 2026
Cited by 1 | Viewed by 1548
Abstract
Background and Objectives: Recent evidence demonstrates additional survival benefit of immune checkpoint inhibitor (ICI) therapy in the treatment of head and neck squamous cell carcinoma (HNSCSC) and nasopharyngeal carcinoma (NPC). However, overall outcomes remain relatively stagnant despite this significant progress. Therapeutic vaccines are [...] Read more.
Background and Objectives: Recent evidence demonstrates additional survival benefit of immune checkpoint inhibitor (ICI) therapy in the treatment of head and neck squamous cell carcinoma (HNSCSC) and nasopharyngeal carcinoma (NPC). However, overall outcomes remain relatively stagnant despite this significant progress. Therapeutic vaccines are a promising adjunct to existing systemic therapy strategies in HNSCC and NPC. This review aims to summarize current evidence, review ongoing studies, and discuss areas of opportunity and potential future directions of vaccine therapy in this space. Methodology: A comprehensive review of the current literature was conducted through database searches on PubMed and ClinicalTrials.gov. Studies were stratified by tumor type, vaccine delivery platform, and early versus recurrent metastatic (RM) disease. Results: Therapeutic vaccines in combination with ICI for HPV-associated HNSCC have shown the most promise, though modest. Vaccine delivery in HPV-negative HNSCC and NPC are still in early development. Integration of therapeutic vaccines across these tumor types is challenged by immune escape mechanisms, lack of viable targets, and tumor heterogeneity. Conclusions: Early data suggest that therapeutic vaccines in combination with ICIs may offer additional benefit in the treatment of HNSCC and NPC, especially in RM HPV-associated HNSCC. Future efforts should validate these early findings through phase 3 trials. Data regarding therapeutic vaccines combined with chemotherapy or radiation is limited but may also provide additional benefit. Full article
(This article belongs to the Special Issue Therapeutic Cancer Vaccines: Advances, Challenges, and Future Directions)
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