Cancer cell–selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules

Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren T Rosenblum, Peter L Choyke & Hisataka Kobayashi
 

Three major modes of cancer therapy （surgery, radiation and chemotherapy） are the mainstay of modern oncologic therapy. To minimize the side effects of these therapies, molecular-targeted cancer therapies, including armed antibody therapy, have been developed with limited success. In this study, we have developed a new type of molecular-targeted cancer therapy, photoimmunotherapy （PIT）, that uses a target-specific photosensitizer based on a near-infrared （NIR） phthalocyanine dye, IR700, conjugated to monoclonal antibodies （mAbs） targeting epidermal growth factor receptors. Cell death was induced immediay after irradiating mAb-IR700–bound target cells with NIR light. We observed in vivo tumor shrinkage after irradiation with NIR light in target cells expressing the epidermal growth factor receptor. The mAb-IR700 conjugates were most effective when bound to the cell membrane and produced no phototoxicity when not bound, suggesting a different mechanism for PIT as compared to conventional photodynamic therapies. Target-selective PIT enables treatment of cancer based on mAb binding to the cell membrane.