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  • Adenoviral Vector-Mediated Monoclonal Antibody Gene Delivery in Cancer Immunotherapy: Opportunities and Challenges

  • Elham Kamalkazemi,1 Parisa Shiri-Aghbash,2 Fereydoon Abedi-Gaballu,3 Nasser Hashemi-Goradel,4 Hossein Banazadeh Baghi,5 Effat Alizadeh,6,*
    1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    2. Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
    3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
    4. Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
    5. Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
    6. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran


  • Introduction: Monoclonal antibodies (mAbs) represent the gold standard in targeted cancer therapy; however, they are associated with several limitations, including high production costs, the requirement for repeated subcutaneous or intravenous injections, and poor penetration into solid tumor tissue. Adenoviral vectors (AdVs) offer promising alternative properties, including the ability to efficiently transduce tumor cells and to achieve sustained, localized expression of therapeutic antibodies. This review aims to evaluate the role of adenoviral vectors as gene delivery vehicles for monoclonal antibody genes in cancer therapy.
  • Methods: A comprehensive literature search was conducted using the PubMed, Scopus, and Web of Science databases. Relevant articles published over recent decades were identified using the following keywords: "adenovirus vector", "monoclonal antibody", "cancer gene therapy", and "immunotherapy". Retrieved studies were systematically analyzed and synthesized.
  • Results: Recombinant adenoviral vectors encoding whole antibodies or their fragments (e.g., scFv, Fab) are able to directly transduce cancer or stromal cells and produce mAbs directly and continuously. This approach has the following advantages: 1) reduced systemic toxicity and treatment cost, 2) the possibility of simultaneous administration of multiple antibodies (e.g., bispecific), 3) induction of a stronger antitumor immune response through activation of T and NK cell populations. Preclinical models in breast, colorectal, and melanoma have demonstrated tumor growth control and increased survival using AdV encoding anti-HER2, anti-CTLA-4, and anti-PD-L1 antibodies. Challenges to be solved in the future are vector self-immunogenicity, insufficient penetration into bulky tumors, and transient expression (due to lack of integration into the host genome).
  • Conclusion: Adenoviral vector-mediated delivery of antibody-encoding genes represents a promising platform for localized cancer immunotherapy. Advances in vector engineering, serotype selection, tumor-specific promoters, and immune-evasion strategies may further improve therapeutic efficacy and safety. Continued preclinical and clinical investigations are required to facilitate successful clinical translation.
  • Keywords: Adenovirus vector, Monoclonal antibody, Cancer immunotherapy, Gene therapy

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