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

Autor:	Kiss B; Department of Urology, Stanford University School of Medicine, Stanford, California.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California., van den Berg NS; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California., Ertsey R; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California., McKenna K; Forty Seven Inc., Menlo Park, California., Mach KE; Department of Urology, Stanford University School of Medicine, Stanford, California.; Veterans Affairs Palo Alto Health Care System, Palo Alto, California., Zhang CA; Department of Urology, Stanford University School of Medicine, Stanford, California., Volkmer JP; Forty Seven Inc., Menlo Park, California., Weissman IL; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California., Rosenthal EL; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California., Liao JC; Department of Urology, Stanford University School of Medicine, Stanford, California. jliao@stanford.edu.; Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Jun 15; Vol. 25 (12), pp. 3561-3571. Date of Electronic Publication: 2019 Mar 19.
DOI:	10.1158/1078-0432.CCR-18-3267
Abstrakt:	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. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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