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Cancers 2017, 9(10), 139; https://doi.org/10.3390/cancers9100139

CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth

1
Promab Biotechnologies, Richmond, CA 94806, USA
2
Forevertek Biotechnology, Changsha 410003, China
3
GenoImmune/a BGI’s Company, Shenzhen 518083, China
4
Antagene Inc., Santa Clara, CA 95054, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Received: 15 September 2017 / Revised: 18 October 2017 / Accepted: 20 October 2017 / Published: 21 October 2017
(This article belongs to the Special Issue CAR-T Cell Therapy against Different Types of Cancer)
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Abstract

CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer. View Full-Text
Keywords: chimeric antigen receptor (CAR); cell therapy; immunotherapy; CD47 tumor antigen; humanized antibody chimeric antigen receptor (CAR); cell therapy; immunotherapy; CD47 tumor antigen; humanized antibody
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Golubovskaya, V.; Berahovich, R.; Zhou, H.; Xu, S.; Harto, H.; Li, L.; Chao, C.-C.; Mao, M.M.; Wu, L. CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth. Cancers 2017, 9, 139.

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