Development and evaluation of a novel antibody-photon absorber conjugate reveals the possibility of photoimmunotherapy-induced vascular occlusion during treatment in vivo
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Yuya Isoda1, Wen Piao1, Eri Taguchi1, Junko Iwano1, Shigeki Takaoka1, Aiko Uchida1, Kiyomi Yoshikawa1, Junichi Enokizono2, Emi Arakawa3, Kazuma Tomizuka1, Yasuhisa Shiraishi1 and Kazuhiro Masuda1
1Research Functions Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd, Machida-shi, Tokyo, Japan
2Translational Research Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd, Suntou-gun, Shizuoka, Japan
3Fuji Research Park, R&D Division, Kyowa Hakko Kirin Co., Ltd, Suntou-gun, Shizuoka, Japan
Kazuhiro Masuda, email: firstname.lastname@example.org
Keywords: antibody-photon absorber conjugate; EpCAM; photoimmunotherapy; vascular occlusion; targeted cancer therapy
Received: May 17, 2018 Accepted: July 13, 2018 Published: July 31, 2018
Photodynamic therapy (PDT) utilize a photosensitizing agent and light for cancer therapy. It exerts anti-cancer effect mainly by inducing vascular occlusion at the irradiated site. By controlling the irradiation area, PDT can be used in a tumor-specific manner. However, the non-specific cellular damage in the surrounding normal tissue is still a serious concern. Photoimmunotherapy (PIT) is a new type of targeted cancer therapy that uses an antibody-photon absorber conjugate (APC). The superiority of PIT to PDT is the improved target specificity, thereby reducing the damage to normal tissues. Here, we developed a novel APC targeting epithelial cell adhesion molecule (EpCAM) as well as a negative control APC that does not bind to the EpCAM antigen. Our in vitro analysis of APC cytotoxicity demonstrated that the EpCAM APC, but not the negative control, was cytotoxic to EpCAM expressing COLO 205 cells after photoirradiation, suggesting that the cytotoxicity is antigen-dependent. However, in our in vivo analysis using a mouse xenograft tumor model, decreased volume of the tumors was observed in all the mice treated with irradiation, regardless of whether they were treated with the EpCAM APC or the negative control. Detailed investigation of the mechanism of these in vivo reveal that both APCs induce vascular occlusion at the irradiation site. Furthermore, the level of vascular occlusion was correlated with the blood concentration of APC, not the tumor concentration. These results imply that, similar to PDT, PIT can also induce non-targeted vascular occlusion and further optimization is required before widespread clinical use.
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