Adding Intratumoral Antibody‐Photoabsorber Conjugate Improves Efficacy of Near‐Infrared Photoimmunotherapy ( NIR ‐ PIT )

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ABSTRACT Near‐infrared photoimmunotherapy (NIR‐PIT) is a new type of cancer treatment that specifically kills target cells while sparing normal tissue. This treatment induces cancer cell death by activating a photoreactive dye with near‐infrared light in an antibody‐photoabsorber conjugate (APC) bound to the cognate target antigen on the tumor cell surface. NIR‐PIT has already been clinically applied in Japan to head and neck cancer patients using an anti‐EGFR antibody‐IR700 dye conjugate, with very promising results. Furthermore, preclinical studies have shown favorable results across many targets and cancer types. To date, APC administration in NIR‐PIT has been performed via intravenous injection. However, some systemic administrations cause side effects. Therefore, local intratumoral injections might be a viable alternative in some cases. Thus, this study aimed to investigate the therapeutic effects of NIR‐PIT following intratumoral administration of APC (IT‐PIT) compared with NIR‐PIT following intravenous administration of APC (IV‐PIT) in various animal models and targets. Intratumoral administration of APC resulted in significantly greater distribution in the target tumor and less in non‐tumor organs, showing that the APC can be efficiently delivered to tumor cells by intratumoral administration. In immunodeficient mice, IT‐PIT showed similar efficacy to IV‐PIT, despite a reduced dose of APC. In immunocompetent mice, IT‐PIT showed a significant effect and extended survival, demonstrating the activation of antitumor immunity, comparable to that of IV‐PIT. These results indicate that IT‐PIT and IV‐PIT are similarly effective in both direct cell killing and in inducing anticancer immune activation, suggesting that intratumoral administration of APC might be a promising new approach in NIR‐PIT.