title: Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules.
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.
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
authors: Makoto
authors: M
authors: Mitsunaga
authors: Mikako
authors: M
authors: Ogawa
authors: Nobuyuki
authors: N
authors: Kosaka
authors: Lauren T
authors: LT
authors: Rosenblum
authors: Peter L
authors: PL
authors: Choyke
authors: Hisataka
authors: H
authors: Kobayashi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D017319:Photosensitizing Agents; D066246:ErbB Receptors