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Cancers (Basel). 2017 Oct 21;9(10). pii: E139. doi: 10.3390/cancers9100139.

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

Author information

1
Promab Biotechnologies, Richmond, CA 94806, USA. vita.gol@promab.com.
2
Promab Biotechnologies, Richmond, CA 94806, USA. Robert.berahovich@promab.com.
3
Promab Biotechnologies, Richmond, CA 94806, USA. huazhou369@gmail.com.
4
Promab Biotechnologies, Richmond, CA 94806, USA. shirley.xu@promab.com.
5
Promab Biotechnologies, Richmond, CA 94806, USA. hizkia.harto@promab.com.
6
Promab Biotechnologies, Richmond, CA 94806, USA. simon.li@promab.com.
7
Forevertek Biotechnology, Changsha 410003, China. simon.li@promab.com.
8
GenoImmune/a BGI's Company, Shenzhen 518083, China. john@promab.com.
9
Antagene Inc., Santa Clara, CA 95054, USA. mikemao@antagene.com.
10
Promab Biotechnologies, Richmond, CA 94806, USA. john@promab.com.

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.

KEYWORDS:

CD47 tumor antigen; cell therapy; chimeric antigen receptor (CAR); humanized antibody; immunotherapy

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