Abstract 949: Boosting oncolytic virus-mediated antitumor immunity by dendritic cell vaccine therapy via p53-activated immune response

Abstract Background: Dendritic cell (DC) vaccine therapy represents a promising immunotherapeutic approach by inducing tumor antigen (TA)-specific immune responses. The tumor suppressor gene p53 is one of the most frequently mutated genes, and mutant or wild-type p53 epitopes function as TAs. Previous studies have demonstrated that DCs transduced with a non-replicative adenovirus expressing wild-type p53 (Ad-p53) (Ad-p53-DCs) induces p53-specific cytotoxic T lymphocytes (CTLs), leading to antitumor immunity. We have previously developed OBP-702, a tumor-specific replication-competent oncolytic adenovirus expressing p53, and demonstrated that OBP-702 exhibits direct cytotoxicity via p53-mediated induction of apoptosis and indirect immune activation via p53-mediated enhancement of immunogenic cell death (ICD). In this study, we investigated whether Ad-p53-DCs or OBP-702-transduced DCs (OBP-702-DCs) in combination with OBP-702 augment antitumor immune responses in murine colorectal cancer models. Methods: Bone marrow-derived DCs were harvested from BALB/c mice and cultured with IL-4 and GM-CSF for five days, followed by infection with Ad-p53 or OBP-702 for two days. Maturation of DCs was evaluated by flow cytometric analysis of surface markers CD11c, CD86, CD103, and MHC-class II. RT-PCR confirmed the expression of p53 RNA in p53-expressing virus-transduced DCs. Ad-p53-DCs or OBP-702-DCs were administered subcutaneously weekly for four cycles before CT26 tumor cell inoculation. Tumor-bearing mice were treated with intratumoral injection of OBP-702 weekly for two cycles. Four experimental groups were established: (1) control, (2) p53-expressing virus-transduced DC alone, (3) OBP-702 alone, and (4) combination of p53-expressing virus-transduced DC and OBP-702. Tumor growth was monitored, and the immune microenvironment was analyzed using immunohistochemistry to evaluate the tumor infiltration of CD8+ T cell and CD11c+ DC. Results: Ad-p53-DCs and OBP-702-DCs displayed significantly increased expression of DC maturation marker compared to control DCs. Combination of Ad-p53-DCs or OBP-702-DCs with OBP-702 markedly suppressed tumor growth compared to OBP-702 monotherapy, demonstrating a synergistic antitumor effect. Immunohistochemical analysis revealed that tumors treated with the combination therapy had significantly increased infiltration of CD8+ T cells and CD11c+ DCs, indicating robust activation of the antitumor immune responses. Conclusions: Our data suggest that immunization with p53-expressing virus-transduced DCs enhances the antitumor efficacy of p53-armed oncolytic adenovirus OBP-702 in murine colorectal cancer models via induction of p53-specific antitumor immune responses. Citation Format: Naohiro Okada, Hiroshi Tazawa, Motohiko Yamada, Satoru Kikuchi, Shinji Kuroda, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara. Boosting oncolytic virus-mediated antitumor immunity by dendritic cell vaccine therapy via p53-activated immune response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 949.