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[Bioinformatic prediction and validation of cellular-mesenchymal epithelial transition(c-Met) as a target for chimeric antigen receptor T (CAR-T) cell therapy in the treatment of colorectal cancer].
Peng, Shang; Min, Jingting; Long, Chirong; Xie, Zilong; Zhang, Lu; Li, Haipeng; Li, Zhenghon.
Afiliação
  • Peng S; Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.
  • Min J; Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.
  • Long C; Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.
  • Xie Z; Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.
  • Zhang L; Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.
  • Li H; Key Laboratory of Basic and Clinical Cardiovascular Disease, Bengbu Medical University, Bengbu 233030, China.
  • Li Z; Department of Physiology, Bengbu Medical University, Bengbu 233030, China. *Corresponding author, E-mail: lizhbbmc@163.com.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(7): 614-622, 2024 Jul.
Article em Zh | MEDLINE | ID: mdl-39179404
ABSTRACT
Objective To explore the potential of the cell surface receptor c-Met as an effective target for chimeric antigen receptor T-cell (CAR-T) therapy in colorectal cancer. Methods The bioinformatics was used to analyze the specific expression of c-Met in colorectal adenocarcinoma (COAD) and its clinical significance. c-Met protein expression was detected by immunohistochemistry in tumor tissues obtained from colorectal cancer patients. Flow cytometry was utilized to assess the expression of c-Met in the HCT116 human colorectal cancer cell line. Additionally, primary T cells isolated from human peripheral blood mononuclear cells (PBMCs) were transduced with a lentivirus to generate second-generation CAR-T cells targeting c-Met, followed by an observation of the inhibitory effects of these c-Met-targeted CAR-T cells on HCT116 cells. Results Immunohistochemistry and bioinformatics data both demonstrated that c-Met was over-expressed in COAD, with patients exhibiting relatively lower expression showing better prognosis. In normal colonic tissue, c-Met was either expressed at low levels or not expressed. Flow cytometry revealed high expression of c-Met in HCT116 cells as well. The c-Met-targeted CAR-T cells were capable of specifically recognizing and targeting antigen-expressing tumor cells. CAR-T cells proliferated specifically under antigenic stimulation, exerting cytotoxic effects on cancer cells and releasing cytokines interleukin 2 (IL-2) and interferon-gamma (IFN-γ), thereby demonstrating the biological functions. Conclusion c-Met may be a promising therapeutic target in COAD; c-Met-targeted CAR-T cells demonstrate inhibitory effects on colorectal cancer cells in vitro.
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Biologia Computacional / Proteínas Proto-Oncogênicas c-met / Receptores de Antígenos Quiméricos Limite: Humans Idioma: Zh Revista: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: China
Buscar no Google
Adicionar na Minha BVS
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PubMed Links

Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Biologia Computacional / Proteínas Proto-Oncogênicas c-met / Receptores de Antígenos Quiméricos Limite: Humans Idioma: Zh Revista: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: China