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

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...

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Published inCancers Vol. 9; no. 10; p. 139
Main Authors Golubovskaya, Vita, Berahovich, Robert, Zhou, Hua, Xu, Shirley, Harto, Hizkia, Li, Le, Chao, Cheng-Chi, Mao, Mike Ming, Wu, Lijun
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 21.10.2017
MDPI
Subjects
Angiogenesis
Antigens
CD47 antigen
CD47 tumor antigen
cell therapy
Cellular biology
Cervical cancer
Cervix
chimeric antigen receptor (CAR)
Chimeric antigen receptors
Cytokines
humanized antibody
Immunoglobulins
immunotherapy
Interleukin 2
Lymphocytes
Lymphocytes T
Metastases
Metastasis
Pancreas
Pancreatic cancer
Phagocytosis
Proteins
Tumor cell lines
Tumors
Xenografts
chimeric antigen receptor (CAR)
CD47 tumor antigen
cell therapy
immunotherapy
humanized antibody
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Summary: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.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers9100139