Abstract
Adenovirus based vectors are commonly used as platforms for therapeutic cancer vaccines due to their high transduction efficiency, large genetic payload capacity, and intrinsic immunostimulatory properties. This systematic review evaluates the safety, immunogenicity, and clinical efficacy of adenovirus-based cancer vaccines in human clinical trials. A comprehensive literature search was conducted according to PRISMA guidelines across PubMed, Scopus, Web of Science, EMBASE, and ClinicalTrials.gov up to February 2026. Twenty clinical trials met the inclusion criteria. Adenoviral vaccines, primarily based on human Ad5 and chimpanzee-derived vectors, were used to deliver tumor-associated antigens and neoantigens. Across studies, these vaccines demonstrated a favorable safety profile, with predominantly mild-to-moderate (grade 1–2) adverse events such as injection-site reactions, flu-like symptoms, and fatigue, while severe toxicities were rare. Immunogenicity outcomes were consistent, with most trials reporting strong antigen-specific CD8⁺ and CD4⁺ T-cell responses. However, clinical efficacy remained limited when used as monotherapy, with modest objective response rates but evidence of disease stabilization and improved survival in some combination strategies. Despite encouraging immunogenicity and safety, the overall clinical benefit of adenoviral vaccines remains constrained by tumor immune evasion and pre-existing vector immunity. Future large-scale randomized trials and rational combination approaches are warranted to enhance their therapeutic potential.
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The authors would like to thank Tabriz University of Medical Sciences for financial support.
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This work was supported by Tabriz University of Medical Sciences, grant number:74557.
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The proposal of this systematic review was approved by the Ethics Committee, Tabriz University of Medical Sciences, Code: IR.TBZMED.AEC.1403.025.
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Kamalkazemi, E., Salehi-Pourmehr, H., Negahdari, B. et al. Adenovirus-based cancer vaccines: a systematic review of clinical trials evidence. Infect Agents Cancer (2026). https://doi.org/10.1186/s13027-026-00784-1
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DOI: https://doi.org/10.1186/s13027-026-00784-1