Targeted Photo-Induced Elimination of Tumor-Associated Macrophages Suppresses Cancer Progression in a Murine Model.

Tumor-associated macrophages (TAMs) are key components of the immunosuppressive tumor microenvironment (TME) and represent attractive therapeutic targets to enhance antitumor immunity. However, systemic TAM-depletion strategies targeting colony-stimulating factor 1 receptor (CSF1R) are associated with the risk of off-target toxicity due to the depletion of macrophages in healthy tissues. Here, we investigated the potential of near-infrared photoimmunotherapy (NIR-PIT) as a strategy for selective, photo-induced elimination of TAMs. The Fab fragment of an anti-CSF1R antibody was conjugated with the photosensitizer IRDye 700DX (IR700), and the therapeutic effects of the conjugate were evaluated in a murine cancer model. Upon NIR light irradiation, Fab-IR700 significantly suppressed tumor growth and improved overall survival of the tumor-bearing mice. Notably, repeated NIR-PIT cycles enhanced therapeutic outcomes and induced durable anticancer effects, as indicated by the rejection of reimplanted cancer cells. Flow cytometry and histological analyses confirmed TAM depletion and significant alterations in the intra-tumoral immune cell populations posttreatment. Overall, CSF1R-targeted NIR-PIT can effectively eliminate TAMs without systemic toxicity, thus presenting a promising strategy to remodel the TME toward an antitumor state and synergize with other immunotherapies against refractory tumors.