Near-Infrared Photochemoimmunotherapy by Photoactivatable Bifunctional Antibody-Drug Conjugates Targeting Human Epidermal Growth Factor Receptor 2 Positive Cancer.

摘要: Near-infrared photoimmunotherapy (NIR-PIT) is a new class of molecular targeted cancer therapy based on antibody–photoabsorber conjugates and NIR light irradiation. Recent studies have shown effective tumor control, including that human epidermal growth factor receptor 2 (HER2)-positive cancer, by selective targeting with NIR-PIT. However, the depth penetration limits its use. Trastuzumab emtansine (T–DM1) an antibody–drug conjugate consisting monoclonal antibody trastuzumab linked to cytotoxic agent maytansinoid DM1. Here, we developed bifunctional antibody–drug–photoabsorber conjugates, T–DM1–IR700, can work as both NIR-PIT chemoimmunotherapy agents. We evaluated feasibility T–DM1–IR700-mediated irradiation comparing in vitro vivo efficacy trastuzumab–IR700 (T–IR700)-mediated HER2-expressing cells. T–IR700 T–DM1–IR700 showed almost identical binding HER2 vivo. Owin...