Abstract

PURPOSE: Near-infrared photoimmunotherapy (NIR-PIT) is a localized molecular cancer therapy combining a photosensitizer-conjugated monoclonal antibody and light energy. CD47 is an innate immune checkpoint widely expressed on bladder cancer cells but absent from luminal normal urothelium. Targeting CD47 for NIR-PIT has the potential to selectively induce cancer cell death and minimize damage to normal urothelium.EXPERIMENTAL DESIGN: The cytotoxic effect of NIR-PIT with anti-CD47-IR700 was investigated in human bladder cancer cell lines and primary human bladder cancer cells derived from fresh surgical samples. Phagocytosis assays were performed to evaluate macrophage activity after NIR-PIT. Anti-CD47-IR700 was administered to murine xenograft tumor models of human bladder cancer for in vivo molecular imaging and NIR-PIT.RESULTS: Cytotoxicity in cell lines and primary bladder cancer cells significantly increased in a light-dose dependent manner with CD47-targeted NIR-PIT. Phagocytosis of cancer cells significantly increased with NIR-PIT compared to antibody alone (p=0.0002). In vivo fluorescence intensity of anti-CD47-IR700 in tumors reached a peak 24-hour post injection and was detectable for at least 14 days. After a single round of CD47-targeted NIR-PIT, treated animals showed significantly slower tumor growth compared to controls (p<0.0001). Repeated CD47-targeted NIR-PIT treatment further slowed tumor growth (p=0.0104) and improved survival compared to controls.CONCLUSION: CD47-targeted NIR-PIT increased direct cancer cell death and phagocytosis resulting in inhibited tumor growth and improved survival in a murine xenograft model of human bladder cancer.

View details for PubMedID 30890547