RRC ID 54113
Author Kim M, Pyo S, Kang CH, Lee CO, Lee HK, Choi SU, Park CH.
Title Folate receptor 1 (FOLR1) targeted chimeric antigen receptor (CAR) T cells for the treatment of gastric cancer.
Journal PLoS One
Abstract Gastric cancer is a malignancy that has a high mortality rate. Although progress has been made in the treatment of gastric cancer, many patients experience cancer recurrence and metastasis. Folate receptor 1 (FOLR1) is overexpressed on the cell surface in over one-third of gastric cancer patients, but rarely is expressed in normal tissue. This makes FOLR1 a potential target for chimeric antigen receptor (CAR) T cell immunotherapy, although the function of FOLR1 has not been elucidated. CAR are engineered fusion receptor composed of an antigen recognition region and signaling domains. T cells expressing CAR have specific activation and cytotoxic effects against cancer cells containing the target antigen. In this study, we generated a CAR that targets FOLR1 composed of a single-chain variable fragment (scFv) of FOLR1 antibody and signaling domains consisting of CD28 and CD3ζ. Both FOLR1-CAR KHYG-1, a natural killer cell line, and FOLR1-CAR T cells recognized FOLR1-positive gastric cancer cells in a MHC-independent manner and induced secretion of various cytokines and caused cell death. Conclusively, this is the first study to demonstrate that CAR KHYG-1/T cells targeting FOLR1 are effective against FOLR1-positive gastric cancer cells.
Volume 13(6)
Pages e0198347
Published 2018-6-6
DOI 10.1371/journal.pone.0198347
PII PONE-D-18-05664
PMID 29874279
PMC PMC5991383
MeSH Animals Cell Line, Tumor Cell Proliferation Cell Survival Folate Receptor 1 / immunology* Humans Immunotherapy, Adoptive / methods* Jurkat Cells K562 Cells Mice Receptors, Antigen, T-Cell / immunology Receptors, Chimeric Antigen / immunology* Recombinant Fusion Proteins / immunology Stomach Neoplasms / immunology Stomach Neoplasms / therapy* T-Lymphocytes / immunology T-Lymphocytes / transplantation* Xenograft Model Antitumor Assays
IF 2.74
Times Cited 14
Human and Animal Cells MKN7(RCB0999) GCIY(RCB0555)