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  • Recombinant oncolytic adenoviruses encoding PD-L1 inhibitors: a novel approach to cancer immunotherapy

  • Nasrin Gholami,1 Amaneh Elikaei,2,* Effat Alizadeh,3 Nasser Hashemi-Goradel,4
    1. Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
    2. Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
    3. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    4. Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran


  • Introduction: Immune checkpoint inhibitor therapies, especially those targeting the PD-1/PD-L1 pathway, have been used to treat cancer. However, their effectiveness is often limited by factors such as a "cold" tumor microenvironment, poor antibody penetration into tumor tissue, and immune-related side effects [1]. In this context, oncolytic adenoviruses, which selectively infect and lyse cancer cells, could serve as gene delivery systems that provide continuous local production of PD-L1 inhibitors at the tumor site while directly destroying tumor cells [2] .
  • Methods: We conducted a comprehensive review of PubMed and Google Scholar using the keywords “oncolytic adenovirus,” “PD-L1 inhibitor,” and “cancer.”
  • Results: Among the retrieved studies, four preclinical studies in which oncolytic adenoviruses directly encoded a PD-L1 inhibitor as an scFv, mini-body, or hybrid Fc peptide were selected for review. In one study, the recombinant virus ZD55-aPD-L1-scFv, which encodes a single-chain variable fragment (scFv) of the anti-PD-L1 antibody, showed a synergistic effect of direct oncolysis and local inhibition of the PD-1/PD-L1 axis in a triple-negative breast cancer model [3]. This effect was significantly superior to the simultaneous administration of the virus and systemic antibody. In another study in a melanoma model, the Ad5Δ24-anti-PD-L1-scFv virus significantly reduced tumor growth and increased cytotoxic lymphocyte infiltration [4].
  • Conclusion: Oncolytic adenoviruses engineered to express PD-L1 inhibitors are a promising platform for overcoming the limitations of current systemic immunotherapies. The combination of direct oncolysis, targeted gene delivery, and local release of immune checkpoint inhibitors could help convert resistant and “cold” tumors into immunotherapy-responsive ones.
  • Keywords: Oncolytic adenovirus, PD-L1 inhibitor, Cancer

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