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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
特异性归巢于肿瘤并介导强效抗肿瘤活性的第三代抗 CD30 CAR-T 细胞
英文原题：The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity.
查看英文原题
The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity.
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中文摘要
CAR-T 细胞疗法对霍奇金淋巴瘤（HL）和间变性大细胞淋巴瘤（ALCL）患者耐受性良好且有效。然而，即使是具有CD28（28z）共刺激结构域的第二代抗CD30 CAR-T 细胞，也未达到预期的完全缓解率。本研究开发了靶向CD30的第二代（CD28z）和第三代（CD28BBz）CAR-T 细胞，并在体内外评估其疗效。CD28z和CD28BBz抗CD30 CAR-T 细胞在扩增、T细胞亚群分布、T细胞活性、效应/记忆表型及耗竭方面相似。但研究发现，28BBz抗CD30 CAR-T 细胞可长期持留、特异性归巢至肿瘤，并在肿瘤异种移植模型中产生强效抗肿瘤活性。研究还显示，第三代抗CD30 CAR-T 细胞副作用较少，致瘤风险可能较低。因此，抗CD30 CAR-T 细胞是治疗霍奇金淋巴瘤的一种安全有效方案。
展开英文摘要原文
CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL).
However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion.
However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis.
Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.
论文信息
- 作者
- Zhang S、Gu C、Huang L、Wu H、Shi J、Zhang Z、Zhou Y、Zhou J
- 第一作者单位
- Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei, 430081, China.China
- 通讯作者单位
- Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei, 430081, China. zhangtongcun@wust.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Scientific reports2022 Jun 21
- 原文标识
- PubMed 35729339 · DOI 10.1038/s41598-022-14523-0
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