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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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Autores principales: Golubovskaya, Vita, Berahovich, Robert, Zhou, Hua, Xu, Shirley, Harto, Hizkia, Li, Le, Chao, Cheng-Chi, Mao, Mike Ming, Wu, Lijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664078/
https://www.ncbi.nlm.nih.gov/pubmed/29065481
http://dx.doi.org/10.3390/cancers9100139
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author Golubovskaya, Vita
Berahovich, Robert
Zhou, Hua
Xu, Shirley
Harto, Hizkia
Li, Le
Chao, Cheng-Chi
Mao, Mike Ming
Wu, Lijun
author_facet Golubovskaya, Vita
Berahovich, Robert
Zhou, Hua
Xu, Shirley
Harto, Hizkia
Li, Le
Chao, Cheng-Chi
Mao, Mike Ming
Wu, Lijun
author_sort Golubovskaya, Vita
collection PubMed
description 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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spelling pubmed-56640782017-11-06 CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth Golubovskaya, Vita Berahovich, Robert Zhou, Hua Xu, Shirley Harto, Hizkia Li, Le Chao, Cheng-Chi Mao, Mike Ming Wu, Lijun Cancers (Basel) Article 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. MDPI 2017-10-21 /pmc/articles/PMC5664078/ /pubmed/29065481 http://dx.doi.org/10.3390/cancers9100139 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Golubovskaya, Vita
Berahovich, Robert
Zhou, Hua
Xu, Shirley
Harto, Hizkia
Li, Le
Chao, Cheng-Chi
Mao, Mike Ming
Wu, Lijun
CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth
title CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth
title_full CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth
title_fullStr CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth
title_full_unstemmed CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth
title_short CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth
title_sort cd47-car-t cells effectively kill target cancer cells and block pancreatic tumor growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664078/
https://www.ncbi.nlm.nih.gov/pubmed/29065481
http://dx.doi.org/10.3390/cancers9100139
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