• Oncolytic Adenovirus Expressing IL-2: An Emerging Approach for Cancer Immunotherapy
  • Elham kamalkazemi,1 Nasser Hashemi Goradel,2 Effat alizadeh,3,*
    1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
    2. Department of Medical Biotechnology, Maragheh University of Medical Sciences, Maragheh, Iran
    3. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran


  • Introduction: Cancer immunotherapy has revolutionized cancer treatment, demonstrating remarkable potential for a wide range of cancer types. Activating the tumor-fighting immune response is crucial for restricting tumor cell growth and proliferation. Among the different immunotherapy strategies, engineered oncolytic adenoviruses as an innovative strategy is used to enhance antitumor immune responses. These modified viruses combat cancer through two main mechanisms: directly destroying cancerous cells and stimulating an immune response to impede tumor progression. Engineered to replicate only in tumor cells, oncolytic adenoviruses specifically target and kill tumor cells and release tumor-specific agents that help create an immune-activating microenvironment. Therefore, they can be engineered to be used as an efficient vehicle for delivering immunomodulatory agents—such as cytokines, antigens, and other transgenes—into the tumor microenvironment (TME). Interleukin-2 (IL-2) is one of the most extensively studied cytokines in cancer therapy. This multifunctional protein promotes the growth and activation of T cells, enhances the proliferation of immune cells, and ultimately improves the overall immune response against cancer. In this review, we will highlight recent advancements in the engineering of adenoviral vectors to specifically express IL-2 in cancer cells to stimulate immune responses.
  • Methods: We conducted a comprehensive literature review of previous studies and collected data of recent 25 years (from 2000 to 2025) using the PubMed and Google Scholar databases. Our query words were “cancer” “oncolytic adenovirus”, “Interleukin-2 (IL-2)”, AND “immunotherapy”.
  • Results: According to the results obtained from studies, the combination of interleukin-2 (IL-2) with adenovirus could increase the frequency of both CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) and enhance solenocyte proliferation. This suggests that these cytokines play a crucial role in T cell activation and proliferation. Also, the mentioned strategy works well in terms of anti-tumor immune responses.
  • Conclusion: The engineering of oncolytic adenoviruses to express IL-2 represents a potential advancement in cancer immunotherapy. By harnessing the dual mechanisms of direct tumor lysis and immune activation, this approach holds significant promise for enhancing patient outcomes in various cancer types.
  • Keywords: Oncolytic adenovirus, Interleukin-2, Cancer, Immunotherapy