Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that uses an antibody-photo-absorber conjugate (APC) composed of a targeting monoclonal antibody conjugated with a photoactivatable phthalocyanine-derivative dye, IRDye700DX (IR700). APCs injected into the body can bind to cancer cells where they are activated by local exposure to NIR light typically delivered by a NIR laser. NIR light alters the APC chemical conformation inducing damage to cancer cell membranes, resulting in necrotic cell death within minutes of light exposure. NIR-PIT selectivity kills cancer cells by immunogenic cell death (ICD) with minimal damage to adjacent normal cells thus, leading to rapid recovery by the patient. Moreover, since NIR-PIT induces ICD only on cancer cells, NIR-PIT initiates and activates antitumor host immunity that could be further enhanced when combined with immune checkpoint inhibition. NIR-PIT induces dramatic changes in the tumor vascularity causing the super-enhanced permeability and retention (SUPR) effect that dramatically enhances nanodrug delivery to the tumor bed. Currently, a worldwide Phase 3 study of NIR-PIT for recurrent or inoperable head and neck cancer patients is underway. In September 2020, the first APC and accompanying laser system were conditionally approved for clinical use in Japan. In this review, we introduce NIR-PIT and the SUPR effect and summarize possible applications of NIR-PIT in a variety of cancers.
Highlights
Cancer is the second leading cause of death globally [1]
Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that uses an antibody-photoabsorber conjugate (APC) composed of a targeting monoclonal antibody conjugated with a photoactivatable phthalocyanine-derivative dye, IRDye700DX (IR700)
APCs injected into the body can bind to cancer cells where they are activated by local exposure to NIR light typically delivered by a NIR laser
Summary
Cancer is the second leading cause of death globally [1]. It is estimated that 19.3 million new cancer cases and almost 10.0 million cancer deaths occurred in 2020. Each method can reduce cancer burden, each treatment causes severe collateral damage to normal cells including immune cells and stem cells contributing to disease recurrence and delayed healing, and resulting in significant consequences for quality of life. The effectiveness of immunotherapy depends on altering the careful balance of effector T cells and immune suppressor cells [4]. It can produce spectacular results, the overall response rate of immunotherapy remains relatively low, mostly because of the absence of T cell infiltration in tumors [5]. Near-infrared photoimmunotherapy (NIR-PIT) is proposed as a method to overcome these challenges. We discuss possible clinical applications of NIR-PIT and SUPR to cancers arising in various organs
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