Abstract B054: Enhanced Antitumor Efficacy of Oncolytic Adenovirus Co-Expressing IL-12 and shVEGF Combined with Anti-PD-1 in Renal Cell Carcinoma

Abstract Despite advancements in treatment modalities such as surgery, chemotherapy, and immunotherapy, resistance remains a formidable challenge in effectively managing renal cell carcinoma (RCC). Although combination therapy with immune checkpoint inhibitors is recommended as a first-line treatment for metastatic renal cell carcinoma (mRCC), it often induces a high incidence of immune-mediated adverse effects. Recently, oncolytic adenoviruses have emerged as promising agents that can enhance the tumor microenvironment and stimulate tumor-specific T cell responses. Therefore, we evaluated the antitumor efficacy of oAd/IL-12/shVEGF—an oncolytic adenovirus co-expressing cytokine interleukin-12 (IL-12) and short hairpin RNA targeting vascular endothelial growth factor (shVEGF)—as a monotherapy and in combination with anti-PD-1 in a renal cell carcinoma mouse model. To investigate the therapeutic potential of oAd/IL-12/shVEGF, we evaluated its efficacy as a monotherapy in a xenograft A498 mouse model and in combination with anti-PD-1 in a syngeneic RENCA mouse model. Tumor-bearing mice were injected intratumorally with oAd/IL-12/shVEGF when the tumors reached 100-200mm³. Tumor volume and body weight were recorded until the end of the experiment. Mice were sacrificed when the tumors reached 1800mm³, and the tumors were disaggregated. To further evaluate the anti-tumor efficacy mediated by oAd/IL-12/shVEGF, tumor tissues were examined for proliferation marker (PCNA), adenovirus injection marker (E1A), and anti-tumor immune marker (CD4/CD8) by H&E and immunohistochemical analysis. In the A498 xenograft mouse model, the oAd/IL-12/shVEGF monotherapy group demonstrated significant tumor growth suppression compared to the PBS-treated group. Additionally, in the RENCA RCC syngeneic mouse model, superior antitumor effects were observed in the group treated with the combination of oAd/IL-12/shVEGF and anti-PD-1 compared to the groups treated with oAd/IL-12/shVEGF or anti-PD-1 alone. Citation Format: Yunlim Kim, A-Rum Yoon, Chae-Ok Yun, Choung-Soo Kim, Bumjin Lim. Enhanced Antitumor Efficacy of Oncolytic Adenovirus Co-Expressing IL-12 and shVEGF Combined with Anti-PD-1 in Renal Cell Carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B054.