論文 - 詳細
| RRC ID | 78834 |
|---|---|
| 著者 | Kinoshita S, Ishii M, Ando J, Kimura T, Yamaguchi T, Harada S, Takahashi F, Nakashima K, Nakazawa Y, Yamazaki S, Ohshima K, Takahashi K, Nakauchi H, Ando M. |
| タイトル | Rejuvenated iPSC-derived GD2-directed CART Cells Harbor Robust Cytotoxicity Against Small Cell Lung Cancer. |
| ジャーナル | Cancer Res Commun |
| Abstract |
UNLABELLED:Small cell lung cancer (SCLC) is exceptionally aggressive, with limited treatment options. Disialoganglioside (GD2) is highly expressed on SCLC and is considered a good target for chimeric antigen receptor (CAR) T cells (CART). Although GD2-directed CARTs (GD2-CART) exhibit cytotoxicity against various GD2-expressing tumors, they lack significant cytotoxicity against SCLC. To enhance cytotoxicity of GD2-CARTs against SCLC, we introduced GD2-CAR into induced pluripotent stem cells (iPSC)-derived rejuvenated cytotoxic T lymphocytes (GD2-CARrejT). GD2-CARrejTs acted much more strongly against SCLC cells than did GD2-CARTs both in vitro and in vivo. Single-cell RNA sequencing elucidated that levels of expression of TIGIT were significantly lower and levels of expression of genes associated with cytotoxicity were significantly higher in GD2-CARrejTs than those in GD2-CARTs. Dual blockade of TIGIT and programmed death-1 (PD-1) increased the cytotoxicity of GD2-CARTs to some extent, suggesting that low TIGIT and PD-1 expression by GD2-CARrejTs is a major factor required for robust cytotoxicity against SCLC. Not only for robust cytotoxicity but also for availability as "off-the-shelf" T-cell therapy, iPSC-derived GD2-CARrejTs are a promising novel treatment for SCLC. SIGNIFICANCE:This research introduces iPSC-derived rejuvenated GD2-CARTs (GD2-CARrejT) as a novel approach to combat SCLC. Compared with conventional GD2-CARTs, GD2-CARrejTs with reduced TIGIT and PD-1 expression demonstrate robust cytotoxicity against SCLC and would be a promising therapy for SCLC. |
| 巻・号 | 4(3) |
| ページ | 723-737 |
| 公開日 | 2024-3-11 |
| DOI | 10.1158/2767-9764.CRC-23-0259 |
| PII | 734784 |
| PMID | 38380966 |
| PMC | PMC10926899 |
| MeSH | Humans Immunotherapy, Adoptive Induced Pluripotent Stem Cells* Lung Neoplasms* Programmed Cell Death 1 Receptor Small Cell Lung Carcinoma* |
| リソース情報 | |
| ヒト・動物細胞 | LA-N-5(RCB0485) T98G(RCB1954) |