Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody

• DOI: 10.1016/j.omto.2022.12.009
• Publication Date: 2023-01-02T16:47:06Z
• Authors: Makiko Sasaki; Mamoru Tanaka; Yuki Kojima; Hirotada Nishie; Takaya Shimura; Eiji Kubota; Hiromi Kataoka
• Keywords: anti-PD-1 antibody; 0303 health sciences; 03 medical and health sciences; photodynamic therapy; immunogenic cell death; talaporfin sodium; immune checkpoint inhibitor; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Original Article; RC254-282; 3. Good health

Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform a basic analysis of the anti-tumor effect of talaporfin sodium (TS)-PDT as well as its synergism with the immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate the cell death mechanism induced by TS-PDT and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT in vitro. We establish a syngeneic mouse model of bilateral flank tumors and verify the enhancement of the abscopal effect on the non-irradiated side. TS-PDT induced apoptosis, necrosis, and autophagy-associated cell death in vitro. TS-PDT induced the release and/or expression of DAMPs in vitro. Tumor growth was inhibited in the TS-PDT and anti-PD-1 antibody combination group compared with other single-treatment or non-treatment groups in vivo. In summary, TS-PDT induces the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhances the anti-tumor immunity induced by TS-PDT. Thus, our results demonstrate that the combination of TS-PDT and anti-PD-1 antibody can potentially be used for anti-tumor therapy.