Photoimmunotherapy targeting biliary‐pancreatic cancer with humanized anti‐TROP2 antibody

Photoimmunotherapy (PIT) is a new type of tumor‐specific treatment utilizing monoclonal antibody (mAb)‐photosensitizer conjugates and near‐infrared (NIR) light irradiation. One potential PIT target, the type I transmembrane protein TROP2, is expressed at high levels in many cancers, including pancreatic carcinoma (PC) and cholangiocarcinoma (CC), in which its expression is correlated with poor prognosis and tumor aggressiveness. In this study, we assessed the efficacy of PIT utilizing newly developed humanized anti‐TROP2 mAb conjugated to the photosensitizer IR700 (TROP2‐IR700) for PC and CC. Immunohistochemistry on PC and CC tissue microarrays confirmed that TROP2 is overexpressed in about half of PC and CC specimens. Using cultured PC and CC cells, TROP2‐IR700 localized TROP2‐specific and target‐specific cell killing was observed after NIR light irradiation. In addition, TROP2‐IR700 was localized to mouse xenograft tumors expressing TROP2 after intravenous injection. PC and CC xenograft tumor growth was significantly inhibited by TROP2‐targeted PIT relative to controls. The efficacy of TROP2‐targeted PIT in vitro and against xenografted tumors in vivo suggests promise as a therapy for human PC and CC, both of which currently have dismal prognoses and limited therapeutic options. The recently developed photoimmunotherapy (PIT) method targets and disrupts cancer cell membranes by combining monoclonal antibody (mAb)‐based targeting with a photosensitizer IR700. By using newly developed humanized anti‐TROP2 mAb conjugated to the IR700 (TROP2‐IR700), both pancreatic cancer and cholangiocarcinoma cells were successfully treated with near‐infrared light both in vitro and in vivo. Given that there is no molecular‐targeted therapy in the standard of care for pancreatic cancer and cholangiocarcinoma patients, TROP2‐targeted PIT is an attractive candidate for clinical trials and ultimately treatment.