c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer

Chimeric antigen receptor (CAR) technology has been highlighted in recent years as a new therapeutic approach for cancer treatment. Although the impressive efficacy of CAR-based T cell adoptive immunotherapy has been observed in hematologic cancers, limited effect has been reported on solid tumors....

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Autores principales:	Chung Hyo Kang, Yeongrin Kim, Da Yeon Lee, Sang Un Choi, Heung Kyoung Lee, Chi Hoon Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	c-Met gastric cancer chimeric antigen receptor CAR T cell KHYG-1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4e930a34791241efa97791db3c2d74d0
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spelling	oai:doaj.org-article:4e930a34791241efa97791db3c2d74d02021-11-25T17:03:28Zc-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer10.3390/cancers132257382072-6694https://doaj.org/article/4e930a34791241efa97791db3c2d74d02021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5738https://doaj.org/toc/2072-6694Chimeric antigen receptor (CAR) technology has been highlighted in recent years as a new therapeutic approach for cancer treatment. Although the impressive efficacy of CAR-based T cell adoptive immunotherapy has been observed in hematologic cancers, limited effect has been reported on solid tumors. Approximately 20% of gastric cancer (GC) patients exhibit a high expression of c-Met. We have generated an anti c-Met CAR construct that is composed of a single-chain variable fragment (scFv) of c-Met antibody and signaling domains consisting of CD28 and CD3ζ. To test the CAR construct, we used two cell lines: the Jurkat and KHYG-1 cell lines. These are convenient cell lines, compared to primary T cells, to culture and to test CAR constructs. We transduced CAR constructs into Jurkat cells by electroporation. c-Met CAR Jurkat cells secreted interleukin-2 (IL-2) only when incubated with c-Met positive GC cells. To confirm the lytic function of CAR, the CAR construct was transduced into KHYG-1, a NK/T cell line, using lentiviral particles. c-Met CAR KHYG-1 showed cytotoxic effect on c-Met positive GC cells, while c-Met negative GC cell lines were not eradicated by c-Met CAR KHYG-1. Based on these data, we created c-Met CAR T cells from primary T cells, which showed high IL-2 and IFN-γ secretion when incubated with the c-Met positive cancer cell line. In an in vivo xenograft assay with NSG bearing MKN-45, a c-Met positive GC cell line, c-Met CAR T cells effectively inhibited the tumor growth of MKN-45. Our results show that the c-Met CAR T cell therapy can be effective on GC.Chung Hyo KangYeongrin KimDa Yeon LeeSang Un ChoiHeung Kyoung LeeChi Hoon ParkMDPI AGarticlec-Metgastric cancerchimeric antigen receptorCAR T cellKHYG-1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5738, p 5738 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	c-Met gastric cancer chimeric antigen receptor CAR T cell KHYG-1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	c-Met gastric cancer chimeric antigen receptor CAR T cell KHYG-1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chung Hyo Kang Yeongrin Kim Da Yeon Lee Sang Un Choi Heung Kyoung Lee Chi Hoon Park c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
description	Chimeric antigen receptor (CAR) technology has been highlighted in recent years as a new therapeutic approach for cancer treatment. Although the impressive efficacy of CAR-based T cell adoptive immunotherapy has been observed in hematologic cancers, limited effect has been reported on solid tumors. Approximately 20% of gastric cancer (GC) patients exhibit a high expression of c-Met. We have generated an anti c-Met CAR construct that is composed of a single-chain variable fragment (scFv) of c-Met antibody and signaling domains consisting of CD28 and CD3ζ. To test the CAR construct, we used two cell lines: the Jurkat and KHYG-1 cell lines. These are convenient cell lines, compared to primary T cells, to culture and to test CAR constructs. We transduced CAR constructs into Jurkat cells by electroporation. c-Met CAR Jurkat cells secreted interleukin-2 (IL-2) only when incubated with c-Met positive GC cells. To confirm the lytic function of CAR, the CAR construct was transduced into KHYG-1, a NK/T cell line, using lentiviral particles. c-Met CAR KHYG-1 showed cytotoxic effect on c-Met positive GC cells, while c-Met negative GC cell lines were not eradicated by c-Met CAR KHYG-1. Based on these data, we created c-Met CAR T cells from primary T cells, which showed high IL-2 and IFN-γ secretion when incubated with the c-Met positive cancer cell line. In an in vivo xenograft assay with NSG bearing MKN-45, a c-Met positive GC cell line, c-Met CAR T cells effectively inhibited the tumor growth of MKN-45. Our results show that the c-Met CAR T cell therapy can be effective on GC.
format	article
author	Chung Hyo Kang Yeongrin Kim Da Yeon Lee Sang Un Choi Heung Kyoung Lee Chi Hoon Park
author_facet	Chung Hyo Kang Yeongrin Kim Da Yeon Lee Sang Un Choi Heung Kyoung Lee Chi Hoon Park
author_sort	Chung Hyo Kang
title	c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
title_short	c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
title_full	c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
title_fullStr	c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
title_full_unstemmed	c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
title_sort	c-met-specific chimeric antigen receptor t cells demonstrate anti-tumor effect in c-met positive gastric cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4e930a34791241efa97791db3c2d74d0
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c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer

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