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 immediately 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.
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This research was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research. We would like to thank C. Regino, T. Hirano and C. Paik for their technical support.
The authors declare no competing financial interests.
Supplementary Figures 1–8 and Supplementary Methods (PDF 878 kb)
Real-time observation of Tra-IR700 mediated phototoxic cell death. (MOV 443 kb)
Real-time observation of Tra-IR700 mediated phototoxic cell death. (MOV 347 kb)
Target specific phototoxicity in response to Tra-IR700 mediated photoimmunotherapy in vitro. (MOV 374 kb)
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Mitsunaga, M., Ogawa, M., Kosaka, N. et al. Cancer cell–selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat Med 17, 1685–1691 (2011). https://doi.org/10.1038/nm.2554
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