Near-Infrared Photoimmunotherapy (NIR-PIT) in Urologic Cancers.

Abstract

Simple SummaryNear-infrared photoimmunotherapy (NIR-PIT) is a novel molecularly-targeted therapy that induces rapid cancer cell death by systemically administering an antibody-photoabsorber conjugate (APC) that binds to cancer cells and irradiating NIR light that drives photochemical transformations of the APC. APCs are constructed by using a monoclonal antibody targeting a cancer cell surface antigen and conjugating it to IRDye700DX silica-phthalocyanine dye. NIR-PIT can selectively kill cancer cells while leaving normal tissues unaffected. Moreover, NIR-PIT activates anti-cancer immunity through the induction of immunogenic cell death of cancer cells. Currently, NIR-PIT is being applied clinically in head and neck squamous cell carcinoma. In previous preclinical studies, NIR-PIT showed excellent efficacy against urologic cancers including bladder cancer and prostate cancer. The clinical application of NIR-PIT will expand to urologic cancers in the near future.Near-infrared photoimmunotherapy (NIR-PIT) is a novel molecularly-targeted therapy that selectively kills cancer cells by systemically injecting an antibody-photoabsorber conjugate (APC) that binds to cancer cells, followed by the application of NIR light that drives photochemical transformations of the APC. APCs are synthesized by selecting a monoclonal antibody that binds to a receptor on a cancer cell and conjugating it to IRDye700DX silica-phthalocyanine dye. Approximately 24 h after APC administration, NIR light is delivered to the tumor, resulting in nearly-immediate necrotic cell death of cancer cells while causing no harm to normal tissues. In addition, NIR-PIT induces a strong immunologic effect, activating anti-cancer immunity that can be further boosted when combined with either immune checkpoint inhibitors or immune suppressive cell-targeted (e.g., regulatory T cells) NIR-PIT. Currently, a global phase III study of NIR-PIT in recurrent head and neck squamous cell carcinoma is ongoing. The first APC and NIR laser systems were approved for clinical use in September 2020 in Japan. In the near future, the clinical applications of NIR-PIT will expand to other cancers, including urologic cancers. In this review, we provide an overview of NIR-PIT and its possible applications in urologic cancers.