4.5 Article

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

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MOLECULAR THERAPY-ONCOLYTICS
卷 28, 期 -, 页码 -

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CELL PRESS
DOI: 10.1016/j.omto.2022.12.009

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photodynamic therapy; talaporfin sodium; immunogenic cell death; immune checkpoint inhibitor; anti-PD-1 antibody

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Photodynamic therapy (PDT) is an anti-cancer therapy that uses a photosensitizer and specific light irradiation. The combination of TS-PDT and anti-PD-1 antibody shows potential in enhancing anti-tumor immunity. TS-PDT induces cell death and the release/expression of damage-associated molecular patterns (DAMPs) in vitro. In mouse models, the combination treatment inhibits tumor growth compared to single treatments or non-treatment groups.
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 performed 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 estimated the cell death mechanism induced by TS-PDT, and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT in vitro. We established syngeneic mouse models of bilateral flank tumors and verified 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 induced the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhanced 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.

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