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Near infrared photoimmunotherapy (NIR-PIT) is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IRDye700DX (IR700), to a monoclonal antibody (mAb) targeting cell-surface molecules. NIR-PIT targeting EGFR using the cetuximab-IR700 conjugate is now in transition to fast-track global Phase 3 clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highly-selective necrotic/immunogenic cell death (ICD) only in target-positive, mAb-IR700-bound cancer cells. This cell death occurs as early as 1 minute after exposure to NIR light. Meanwhile, immediately adjacent target-negative cells are unharmed. ICD induced by NIR-PIT promoted maturation of immature dendritic cells (DCs) to maturated DCs that primed cytotoxic T-cells to react with cancer-related antigens released from crashed cancer cells. Inhibition of immuno-checkpoints including PD-1/PD-L1 axis or CTLA-4 is one of several major methods for enhancing cytotoxicity of tumor-infiltrating T-cells. In this talk, I will focus on NIR-PIT combined with an immune-checkpoint inhibitor that could treat not only local tumors but also distant untreated tumors without recurrence in some syngeneic cancer models. Additionally, NIR-PIT combined with local tumor-infiltrating negative-regulatory T-cells by CD25-targeted NIR-PIT that is another major methods for enhancing cytotoxicity of tumor-infiltrating T-cells similarly operated in different tumor models. The regimens of NIR-PIT combined with methods for enhancing host tumor immunity could cure primary and metastatic tumor and yield vaccination effect against treated cancer cells that would be the ultimate form of NIR-PIT in oncology clinic.
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