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Clin Cancer Res. 2019 Jun 15;25(12):3561-3571. doi: 10.1158/1078-0432.CCR-18-3267. Epub 2019 Mar 19.

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

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Department of Urology, Stanford University School of Medicine, Stanford, California.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California.
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California.
Forty Seven Inc., Menlo Park, California.
Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Department of Urology, Stanford University School of Medicine, Stanford, California.



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 in vivo 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 (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.


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.

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