CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于 GAS6 的 CAR-T 细胞对胰腺癌表现出强效抗肿瘤活性
英文原题：GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer.
查看英文原题
GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
我们的研究结果表明，GAS6-CAR-T 细胞疗法可能对胰腺癌有效且毒性较低。
研究思路结论见上方概要
背景
受体酪氨酸激酶TAM家族（TYRO3、AXL和MERTK）在多种癌细胞和肿瘤相关巨噬细胞中高表达，并促进包括胰腺肿瘤在内的癌症发展。靶向TAM受体可能是一种有前景的治疗选择。
方法
我们设计了一种基于生长停滞特异性蛋白6（GAS6）胞外域的新型CAR，GAS6是所有TAM成员的天然配体。在体外和体内测试了CAR-T 杀伤胰腺癌细胞的能力，并在小鼠和非人灵长类动物中评估了安全性。
结果
GAS6-CAR-T 细胞在体外能有效杀伤TAM阳性胰腺癌细胞系、吉西他滨耐药癌细胞和癌症干细胞样细胞。GAS6-CAR-T 细胞还显著抑制了小鼠体内PANC1异种移植瘤和患者来源异种移植瘤的生长。此外，尽管已证实该CAR能识别小鼠TAM，这些CAR-T 细胞在非人灵长类或小鼠中未引起明显副作用。
展开英文摘要原文
BACKGROUND
The receptor tyrosine kinases TAM family (TYRO3, AXL, and MERTK) are highly expressed in multiple forms of cancer cells and tumor-associated macrophages and promote the development of cancers including pancreatic tumor. Targeting TAM receptors could be a promising therapeutic option.
METHODS
We designed a novel CAR based on the extracellular domain of growth arrest-specific protein 6 (GAS6), a natural ligand for all TAM members. The ability of CAR-T to kill pancreatic cancer cells is tested in vitro and in vivo, and the safety is evaluated in mice and nonhuman primate.
RESULTS
GAS6-CAR-T cells efficiently kill TAM-positive pancreatic cancer cell lines, gemcitabine-resistant cancer cells, and cancer stem-like cells in vitro. GAS6-CAR-T cells also significantly suppressed the growth of PANC1 xenografts and patient-derived xenografts in mice. Furthermore, these CAR-T cells did not induce obvious side effects in nonhuman primate or mice although the CAR was demonstrated to recognize mouse TAM.
CONCLUSIONS
Our findings indicate that GAS6-CAR-T-cell therapy may be effective for pancreatic cancers with low toxicity.
论文信息
- 作者
- Fan J、Yu Y、Yan L、Yuan Y、Sun B、Yang D、Liu N、Guo J
- 第一作者单位
- Division of Abdominal Tumor Multimodality Treatment and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.China
- 通讯作者单位
- Division of Abdominal Tumor Multimodality Treatment and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. zhaoxudong@wchscu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Journal of hematology & oncology2023 Jul 20
- 原文标识
- PubMed 37475048 · DOI 10.1186/s13045-023-01467-9
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →