CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer

• Published in: Clinical cancer research Vol. 25; no. 12; pp. 3561 - 3571
• Main Authors: Kiss, Bernhard, van den Berg, Nynke S, Ertsey, Robert, McKenna, Kelly, Mach, Kathleen E, Zhang, Chiyuan Amy, Volkmer, Jens-Peter, Weissman, Irving L, Rosenthal, Eben L, Liao, Joseph C
• Format: Journal Article
• Language: English
• Published: United States 15.06.2019
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-18-3267

Near-infrared photoimmunotherapy (NIR-PIT) is a localized molecular cancer therapy combining a photosensitizer-conjugated mAb 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. 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 molecular imaging and NIR-PIT. 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 with antibody alone ( = 0.0002). fluorescence intensity of anti-CD47-IR700 in tumors reached a peak 24-hour postinjection 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 with controls ( < 0.0001). Repeated CD47-targeted NIR-PIT treatment further slowed tumor growth ( = 0.0104) and improved survival compared with controls. 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.