c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
| العنوان: | c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer |
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| المؤلفون: | Yeongrin Kim, Heung Kyoung Lee, Chung Hyo Kang, Chi Hoon Park, Da Yeon Lee, Sang Un Choi |
| المصدر: | Cancers Volume 13 Issue 22 Cancers, Vol 13, Iss 5738, p 5738 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, C-Met, T cell, Jurkat cells, Article, chemistry.chemical_compound, medicine, Cytotoxic T cell, RC254-282, c-Met, biology, chimeric antigen receptor, Chemistry, gastric cancer, CAR T cell, CD28, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, KHYG-1, Chimeric antigen receptor, medicine.anatomical_structure, Oncology, Cell culture, biology.protein, Cancer research, Antibody, human activities |
| الوصف: | Simple Summary c-Met is known to be overexpressed in gastric cancers. Here, we developed anti-c-Met CAR T cell and measured its anti-tumor efficacy in vitro and in vivo. Our anti c-Met CAR T cells have shown selective killing of c-Met overexpressed gastric cancer cells. Based on our results, we suggest that anti-c-Met CAR T cell therapy could be effective for gastric cancer patients. Abstract 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| DOI: | 10.3390/cancers13225738 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d2bba053488e77b1703929a0b7fd970 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0d2bba053488e77b1703929a0b7fd970 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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| DOI: | 10.3390/cancers13225738 |