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CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer.


ABSTRACT: PURPOSE: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. 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 with antibody alone (P = 0.0002). In vivo 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 (P < 0.0001). Repeated CD47-targeted NIR-PIT treatment further slowed tumor growth (P = 0.0104) and improved survival compared with controls. CONCLUSIONS: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.

SUBMITTER: Kiss B 

PROVIDER: S-EPMC7039531 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer.

Kiss Bernhard B   van den Berg Nynke S NS   Ertsey Robert R   McKenna Kelly K   Mach Kathleen E KE   Zhang Chiyuan Amy CA   Volkmer Jens-Peter JP   Weissman Irving L IL   Rosenthal Eben L EL   Liao Joseph C JC  

Clinical cancer research : an official journal of the American Association for Cancer Research 20190319 12


<h4>Purpose</h4>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.<h4>Experimental design</h4>The cytotoxic effect of NIR-PIT with anti-CD47-IR700 was investig  ...[more]

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