Preserved host immunity with intercellular adhesion molecule-1 (ICAM-1)-targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of triple-negative breast cancer and other malignancies

Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that combines an antibody photoabsorber-conjugate (APC) with NIR light to induce direct cytotoxicity and immunogenic cell death. Intercellular Adhesion Molecule 1 (ICAM-1), a cell surface protein overexpressed in various cancers, is a promising target for cancer therapy. We previously reported that ICAM-1-targeted NIR-PIT could be used in the treatment of ICAM-1 expressing triple-negative breast cancer (TNBC); however, ICAM-1 is also expressed on immune cells within the tumor microenvironment (TME). Therefore, the net impact of ICAM-1-targeted NIR-PIT on the tumor vs. antitumor host immunity remains unclear, posing a significant challenge to its clinical advancement. In this study, we investigated the antitumor effect of ICAM-1-targeted NIR-PIT including its influence on host immunity following NIR light irradiation, using immunocompetent mouse models. In vitro, ICAM-1-targeted NIR-PIT caused immunogenic cell death in EO771 (breast cancer) and SP2/0 (myeloma) models expressing ICAM-1. Ex vivo, ICAM-1-targeted NIR-PIT effectively eliminated ICAM-1-expressing cancer cells and immune cells within the TME. However, the net effect was to suppress tumor progression and prolong survival in EO771, MOC1 (oral carcinoma), and SP2/0 models in vivo. Enhanced antitumor host immunity was observed after ICAM-1-targeted NIR-PIT in the MOC1 model. In conclusion, ICAM-1-targeted NIR-PIT holds promise as a treatment for various cancer models expressing ICAM-1 beyond TNBC by directly killing cancer cells and enhancing host immune response.