| RRC ID |
54113
|
| 著者 |
Kim M, Pyo S, Kang CH, Lee CO, Lee HK, Choi SU, Park CH.
|
| タイトル |
Folate receptor 1 (FOLR1) targeted chimeric antigen receptor (CAR) T cells for the treatment of gastric cancer.
|
| ジャーナル |
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.
|
| 巻・号 |
13(6)
|
| ページ |
e0198347
|
| 公開日 |
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
|
| 引用数 |
14
|
| リソース情報 |
| ヒト・動物細胞 |
MKN7(RCB0999)
GCIY(RCB0555) |
