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
显性负性 TGF-β 受体 2 共表达增强新型 TREM1/DAP12-BB 型 CAR-T 细胞在实体瘤中的治疗疗效
英文原题：Co-Expression of Dominant-Negative TGF-β Receptor 2 Enhances the Therapeutic Efficacy of Novel TREM1/DAP12-BB-Based CAR-T Cells in Solid Tumours.
查看英文原题
Co-Expression of Dominant-Negative TGF-β Receptor 2 Enhances the Therapeutic Efficacy of Novel TREM1/DAP12-BB-Based CAR-T Cells in Solid Tumours.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法治疗血液系统恶性肿瘤效果显著，但其用于实体瘤受到免疫抑制性肿瘤微环境（TME）的限制。本研究设计了一种新型SS1-TREM1/DAP12-BB CAR-T 细胞，用于靶向卵巢癌，并进一步改造使其共表达显性负性TGF-β受体2（DNR），以抵抗TME中的CAR-T 细胞耗竭。DNR可有效阻断TGF-β信号，从而增强CAR-T 细胞在富含TGF-β1环境中的存活和抗肿瘤活性。体内评估显示，共表达DNR增强了TREM1/DAP12-BB CAR-T 细胞的抗肿瘤疗效，并使其能够抵抗肿瘤再次攻击。这些发现凸显了DNR共表达在CAR设计中的广泛潜力，为复发性卵巢癌患者提供了一种新型治疗策略。
展开英文摘要原文
Chimeric antigen receptor (CAR) T-cell therapy has exhibited remarkable efficacy in the treatment of haematological malignancies, yet its application in solid tumours is hindered by the immunosuppressive tumour microenvironment (TME). In this study, a novel SS1-TREM1/DAP12-BB CAR-T cell was devised to target ovarian cancer and further engineered to co-express the dominant-negative TGF- receptor 2 (DNR) to combat CAR-T cell exhaustion in TME.
The incorporation of DNR effectively blocked TGF- signalling, thereby enhancing CAR-T cell survival and antitumor activity in a TGF- 1-rich environment. In vivo evaluations demonstrated that DNR co-expression potentiated the antitumor efficacy of TREM1/DAP12-BB CAR-T cells and conferred resilience against tumour rechallenge.
These findings underscore the broad potential of DNR co-expression in CAR design, presenting a novel therapeutic strategy for patients with recurrent ovarian cancer.
论文信息
- 作者
- Zhu S、Hu J、Lin J、Wang C、Wang E
- 单位
- Nanjing CART Medical Technology Co. Ltd., Nanjing, P.R. China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Immunology2025 Mar
- 原文标识
- PubMed 39746895 · DOI 10.1111/imm.13888