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靶向 CD30 的外周 T 细胞淋巴瘤免疫治疗新策略:基于 CD30 单克隆抗体的 CAR 修饰 T 细胞疗法

英文原题:A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb.

PubMed 2021/01/29(内容时间) Cancer Gene Ther Q1 · IF 6.4(JCR 2025)

研究概要

CAR-T 细胞免疫疗法(CAR-T)在治疗淋巴造血系统来源的肿瘤方面已显示出显著疗效。

中文摘要

CAR-T 细胞免疫治疗(CAR-T)在治疗淋巴系统来源肿瘤方面已显示显著疗效。本研究报告了一种用于复发性恶性 CD30 阳性外周 T 细胞淋巴瘤(PTCL)的 CAR-T 治疗方案。研究者从 PTCL 患者肿瘤组织获取 CD30 胞外片段基因序列,并克隆至质粒载体以表达 CD30 抗原;随后从 CD30 抗原免疫小鼠获得的 CD30 阳性单克隆杂交瘤细胞中制备靶向 CD30 的单链抗体可变片段(scFv)。构建第二代 CAR 慢病毒载体后制备 CD30 CAR-T 细胞,并评估其对 Karpas 299 细胞的细胞毒性。细胞裂解结果显示,9C11-2 CAR-T 细胞在乳酸脱氢酶(LDH)和实时细胞电子传感(RTCA)检测中均显著促进 CD30 阳性 Karpas 299 细胞裂解。体内实验显示,9C11-2 CAR-T 细胞可有效抑制 Karpas 299 细胞异种移植 NCG 小鼠模型的肿瘤生长。CD30 CAR-T 细胞与靶细胞共培养时表现出有效细胞毒作用,静脉注射至 PTCL 异种移植瘤后也显著抑制肿瘤。结果提示,这种新型 CD30 CAR-T 细胞可能成为有前景的肿瘤治疗候选方案。

展开英文摘要原文

Chimeric antigen receptor T-cell immunotherapy (CAR-T) has shown remarkable efficacy in treating tumors of lymphopoietic origin. Herein, we demonstrate an effective CAR-T cell treatment for recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL) has been demonstrated. The extracellular fragment gene sequences of CD30 were obtained from tumor tissues of PTCL patients and cloned into a plasmid vector to express the CD30 antigen. The CD30 targeting single-chain antibody fragment (scFv) was obtained from CD30-positive monoclonal hybridoma cells, which were obtained from CD30 antigen immunized mice. After a second-generation of CAR lentiviral construction, CD30 CAR T cells were produced and used to determine the cytotoxicity of this construct toward Karpas 299 cells. The results of CD30 CAR T-mediated cell lysis show that 9C11-2 CAR T cells could significantly promote the lysis of CD30-positive Karpas 299 cells in both LDH and real-time cell electronic sensing (RTCA) assays. In vivo data show that 9C11-2 CAR T cells effectively suppress the tumor growth in a Karpas 299 cell xenograft NCG mouse model. The CD30 CAR T cells exhibited an efficient cytotoxic effect after being co-cultured with the target cells and they also exhibited a significant tumor-inhibiting ability after being intravenously injected into PTCL xenograft tumors; these observations suggest that the new CD30 CAR-T cell may be a promising therapeutic candidate for cancer therapy.

论文信息

作者
Wu Y、Chen D、Lu Y、Dong SC、Ma R、Tang WY、Wu JQ、Feng JF
第一作者单位
Research Center of Clinical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, P. R. China.China
通讯作者单位
Research Center of Clinical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, P. R. China. wujzh@jszlyy.com.cn.China
文献类型
非美国政府资助研究
期刊
Cancer gene therapy2022 Feb
原文标识
PubMed 33514882 · DOI 10.1038/s41417-021-00295-8