CD47-targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research Kiss, B., van den Berg, N. S., Ertsey, R., McKenna, K., Mach, K. E., Zhang, C. A., Volkmer, J., Weissman, I. L., Rosenthal, E. L., Liao, J. C. 2019


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