CD47 targeted near-infrared photo-immunotherapy: a promising tool combining monoclonal antibodies and photodynamics for treating human bladder cancer
| Autor: | George Bou Kheir, Thierry Roumeguere, Fouad Aoun |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Clin Cancer Res |
| ISSN: | 2223-4691 2223-4683 |
| Popis: | PURPOSE: Near-infrared photoimmunotherapy (NIR-PIT) is a localized molecular cancer therapy combining a photosensitizer-conjugated monoclonal antibody 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 to antibody alone (p=0.0002). In vivo fluorescence intensity of anti-CD47-IR700 in tumors reached a peak 24-hour post injection 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 to controls (p |
| Databáze: | OpenAIRE |
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