Abstract
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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Acknowledgements
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.
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M.M. conducted experiments, performed analysis and wrote the manuscript. M.O., N.K. and L.T.R. conducted experiments and performed analysis. P.L.C. wrote the manuscript and supervised the project. H.K. planned and initiated the project, designed and conducted experiments, wrote the manuscript and supervised the project.
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Supplementary Text and Figures
Supplementary Figures 1–8 and Supplementary Methods (PDF 878 kb)
Supplementary Video 1a
Real-time observation of Tra-IR700 mediated phototoxic cell death. (MOV 443 kb)
Supplementary Video 1b
Real-time observation of Tra-IR700 mediated phototoxic cell death. (MOV 347 kb)
Supplementary Video 2
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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DOI: https://doi.org/10.1038/nm.2554
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