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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.

Author information

1
Department of Urology, Stanford University School of Medicine, Stanford, California.
2
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California.
3
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California.
4
Forty Seven Inc., Menlo Park, California.
5
Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
6
Department of Urology, Stanford University School of Medicine, Stanford, California. jliao@stanford.edu.

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.

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