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

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.