LAUSR

Background: Hydrogen peroxide (H2O2) causes oxidative stress and cytotoxicity and may be used in cancer therapy in combination with radiotherapy (RT). Indeed, H2O2 has been clinically developed as a radiosensitizer (development code: KRC-01). However, effects of H2O2 on antitumor immunity remain unclear. In this study, we investigated the effects, especially an abscopal effect, using mouse models. Material and Method: We used MC-38 (mouse colon cancer) and B16F10 (mouse melanoma) cell lines. Tumor cells were implanted simultaneously in two locations; hind legs and back of mice. A self-made radiation shielding device was used to prevent irradiation of the tumors on the back. Only the hind legs were directly injected with a mixture of H2O2 and hyaluronic acid (KRC-01), and then irradiated. Immune cells in tumors or tumor draining lymph nodes were analyzed with flow cytometry. Result: We compared tumor growth among four groups: control, irradiation alone, H2O2 alone, and combination groups. Compared to the other groups, the combination significantly reduced non-irradiated tumor growth (abscopal effect). In immunodeficient SCID mice, this effect was not observed. Flow cytometric analyses of tumor draining lymph nodes showed that dendritic cells were maturated in the combination groups compared to the others. In addition, CD8+ T cells were activated in the non-irradiated tumors from the combination group compared to the others. Conclusion: Intratumoral H2O2 administration enhanced the abscopal effect through activating antitumor immunity by RT. Citation Format: Naoya Kemmotsu, Li zhu, Youki Ueda, Hiromichi Dansako, Shinichi Toyooka, Joji Nagasaki, Yosuke Togashi. Combined treatment with direct hydrogen peroxide administration and irradiation promotes an abscopal effect in mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1099.