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Photoimmunotherapy (PIT) is a new type of molecular targeted cancer therapy, which allows the selective destruction of cancer cells in mice without any damage to normal tissues. It is a light-based cancer therapy, which was developed by Professor Kobayashi and his colleagues at National Cancer Institute, Bethesda, Maryland.

Photosensitizers are molecules that rapid destroy cells though the production of reactive oxygen species (ROS) when exposed to light at specific wavelength. Conventional photodynamic therapy (PDT) combines a non-specific photosensitizer with non-ionizing light to kill cancer cells. However, this PDT treatment results in serious side effects because non-targeted photosentizer are also taken up by normal tissues.

PIT treatment avoids the side effects problem through the creation of a targeted-photosensitizer, which involves two components: a monoclonal antibody (mAb) which recognizes specific proteins on the surface of cancer cells, and a non-targeted photosentizer. Even though the new mAb-based photosensitizers are distributed throughout the body, it can be activated by light for targeted PIT only when bound to specific proteins on cancer cellular membrane.

The research team at Professor Kobayashi’s lab coupled anti-tumor antibodies targeting human epidermal growth factor receptors to the phthalocyanine dye, IR700, which is activated by near-infrared light. Phthalocyanine was chosen because its hydrophilicity and strong cytotoxicity induced when associated with cellular membrane. A variety of cancers, such as breast and pancreatic caners over-express epidermal growth factor receptors. This new photosensitizing compound was named “IRDye 700DX NHS Ester” or “mAb-IR700 conjugates”.

In Vitro studies showed that mAb-IR700 killed tumor cells seconds after the near-infrared light irradiation. There was also a positive correlation between the intensity of excitation light and percentage of cell death. Infrared light alone or mAb-IR700 conjugate alone did not cause any damage to normal cells. When tumor-xenografted mice were treated with mAb-IR700 and near-infrared light, significant tumor shrinkage was observed. With fractionated administration of mAB–IR700 conjugate followed by systematic repeated NIR light irradiation to the tumor, 80 percent of tumor cells war eradicated and the mice’s survival were significantly prolonged. Based on the current hypothesis, cell death induced by PIT was caused by rapid expansion of local water upon the formation of holes in the membrane.

Another desirable feature of PIT using mAb-IR700 conjugate is that it also emits fluorescence light upon activation. Therefore before PIT, mAb-IR700 can be admited to at lower dosage guide the application of excitation light to tumor tissues, further minimizing unnecessary light exposure to surrounding tissues.

PIT is a promising highly selective and clinically feasible therapeutic method for treatment of mAb-binding tumors with minimal off-target effects. For future directions, researchers are trying to conjugate a variety of other monoclonal antibodies to phthalocyanine, creating a highly flexible therapeutic platform.