Abstract 5971: F3 targeted near-infrared photoimmunotherapy: The ideal therapeutic approach for numerous malignancies

Abstract Introduction: F3 is a cell surface protein that plays a role in blood clotting, but recent research has revealed its implication in cancer proliferation, metastasis, angiogenesis, and immune escape. TCGA cohort analysis has shown that elevated F3 is a common feature of many cancers, and generally correlates with poor patient survival. Therefore, the potential of F3 as a therapeutic target in cancer is worth exploring. Tisotsumab-vedotin, an antibody-drug conjugate (ADC) that targets F3, was approved by the FDA for cervical cancer and is undergoing clinical trials in some solid cancers. However, ADCs may give rise to concerns about drag resistance following cellular internalization. Herein, we developed and tested an F3 targeted near-infrared photoimmunotherapy (NIR-PIT) to overcome some of these resistance mechanisms. Methods: We created a conjugate of tisotumab as an F3 antibody and IR700. The efficacy of F3-targeted NIR-PIT was investigated using multiple cancer cell lines (A431; epidermoid carcinoma, HPAF-II; pancreatic adenocarcinoma, HSC-2; oral carcinoma, HT-1376luc; bladder carcinoma, MDAMB231; breast adenocarcinoma, and SKOV-3; ovarian serous cystadenocarcinoma) in vitro. In vivo, the efficacy of F3-targeted NIR-PIT was evaluated in HPAF-II tumor using xenograft mouse models. In addition, the pathological change after NIR-PIT was also evaluated in A431, HPAF-II, HSC-2, HT-1376luc, MDAMB231, and SKOV-3 tumors. Results: These cell lines showed F3 expression in vitro and in vivo. Additionally, F3 expression was specific to cancer cells in HPAF-II tumor model. In vitro, F3-targeted NIR-PIT damaged the multiple cell lines in an NIR light dose-dependent manner. In vivo, F3-targeted NIR-PIT suppressed tumor growth and improved survival rates compared to the untreated group. Pathologically, A431, HPAF-II, HSC-2, HT1376-luc, MDAMB231 and SKOV-3 tumors after NIR-PIT contain large numbers of necrotic cells that are shown typically less dark nuclei and eosinophilic cytoplasm with some vacuolar degeneration than untreated tumors. Conclusions: F3-targeted NIR-PIT holds the efficacy against multiple cancers expressing F3, regardless of the specific cancer type. Therefore, this modality exhibits significant promise as a potential NIR-PIT option. Citation Format: Seiichiro Takao, Aki Furusawa, Hiroshi Fukushima, Shuhei Okuyama, Makoto Kano, Hiroshi Yamamoto, Peter L. Choyke, Hisataka Kobayashi. F3 targeted near-infrared photoimmunotherapy: The ideal therapeutic approach for numerous malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5971.