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

Makoto Mitsunaga et al. have developed a new form of molecular-targeted cancer therapy that provides an alternative to current photodynamic approaches where damage to surrounding healthy cells and tissues can be a problem. They use a target-specific photosensitizer based on a near-infrared phthalocyanine dye, which is conjugated to monoclonal antibodies targeting human epidermal growth factor receptors (HER1 and HER2). Selective treatment using this approach was shown in vivo in subcutaneous cancer xenografts in mice. 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.