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: Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren T Rosenblum, Peter L Choyke, Hisataka Kobayashi
• Journal: Nature medicine (Nat Med) Vol. 17 Issue 12 Pg. 1685-91 (Nov 06 2011) ISSN: 1546-170X [Electronic] United States
• PMID: 22057348 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Monoclonal
• Photosensitizing Agents
• ErbB Receptors

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Cell Line, Tumor (drug effects)
• Cell Proliferation
• ErbB Receptors (immunology, metabolism)
• Female
• Humans
• Immunotherapy
• Mice
• Mice, Nude
• Microscopy, Fluorescence
• NIH 3T3 Cells
• Neoplasms (therapy)
• Photochemotherapy (methods)
• Photosensitizing Agents (therapeutic use)
• Xenograft Model Antitumor Assays