[Near Infrared Photoimmunotherapy for Cancer]

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 targetingEGFR usingthe cetuximab-IR700 conjugate is now in transition to fast-track global Phase Ⅲ clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highlyselective 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 Tcells to react with cancer-related antigens released from destroyed cancer cells. Inhibition of immuno-checkpoints including PD-1/PD-L1 axis or CTLA-4 is one of several major methods for enhancingcytotoxicity of tumor-infiltratingT -cells. In this section, I will also discuss NIR-PIT combined with an immuno-checkpoint inhibitor that could treat not only local tumors but also distant untreated metastatic tumors without recurrence in some syngeneic cancer models. Additionally, NIR-PIT to a local tumor combined with local tumor-infiltratingneg ative-regulatory T-cells by CD25-targeted NIR-PIT that is another major methods for enhancingcytotoxicity of tumor-infiltratingT -cells similarly operated in different tumor models. The regimens of NIR-PIT combined with methods for enhancinghost 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.