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单倍体相合γδ T 细胞诱导化疗难治性 B 细胞非霍奇金淋巴瘤完全缓解

英文原题:Haploidentical γδ T Cells Induce Complete Remission in Chemorefractory B-cell Non-Hodgkin Lymphoma.

PubMed 2023/01/10(内容时间) J Immunother Q3 · IF 2.9(JCR 2025)

研究概要

慢性淋巴细胞白血病转化为侵袭性淋巴瘤,称为Richter转化,常伴随化疗耐药和高死亡率。

中文摘要

慢性淋巴细胞白血病向侵袭性淋巴瘤的转化,称为Richter转化,常伴随化疗耐药和高死亡率。因此,需要新的治疗策略来成功治疗这些患者。一种可能性是使用CAR-T 细胞的细胞免疫治疗。然而,直到细胞可用的时间延迟以及由于这些患者免疫系统受损导致效应细胞数量有限,可能损害这种方法的疗效。另一种有前景的尝试可能是γδ T细胞治疗。一旦被激活,它们对多种恶性肿瘤表现出各种抗肿瘤效应。此外,它们可以安全地用于异基因环境,并且如临床研究已证明的那样,可以在体内扩增。此外,体外数据显示,γδ T细胞的细胞毒性可以通过单克隆抗体显著增强。在此,我们介绍一位患有Richter转化且对多线免疫化疗无反应的患者。由于缺乏进一步的治疗选择,我们进行了单倍体相合γδ T细胞过继转移联合单克隆抗体obinutuzumab应用的个体化治疗。通过这种治疗方法实现了组织学确认的完全缓解,且未见相关副作用。该病例突出了γδ T细胞的潜力以及这种治疗方法用于进一步临床试验的可行性。

展开英文摘要原文

The transformation of chronic lymphocytic leukemia to an aggressive lymphoma, called Richter transformation, is often accompanied by resistance to chemotherapy and high mortality. Thus, novel therapeutic strategies are required for the successful treatment of these patients. One possibility is cellular immunotherapy with chimeric antigen receptor T cells. However, the time delay until cells are available and the limited number of effector cells due to the impaired immune system of these patients potentially compromises the efficacy of this approach. Another promising attempt might be the therapy with γδ T cells. Once activated, they exhibit various antitumor effects against several types of malignancies. Furthermore, they can be safely used in an allogeneic setting and can be multiplied in vivo as already demonstrated in clinical studies. In vitro data, in addition, show that the cytotoxicity of γδ T cells can be significantly enhanced by monoclonal antibodies. Here we present a patient, who suffered from Richter transformation and did not respond to several lines of immunochemotherapy. Due to the lack of further therapy options, we conducted an individual therapy with adoptive transfer of haploidentical γδ T cells combined with the application of the monoclonal antibody obinutuzumab. A histologically confirmed complete remission was achieved through this therapy approach, whereby relevant side effects were not seen. This case highlights the potential of γδ T cells and the feasibility of this therapeutic approach for further clinical trials.

论文信息

作者
Bold A、Gaertner J、Bott A、Mordstein V、Schaefer-Eckart K、Wilhelm M
单位
Department of Hematology and Medical Oncology.
文献类型
病例报告 · 非美国政府资助研究
期刊
Journal of immunotherapy (Hagerstown, Md. : 1997)2023 Feb-Mar 01
原文标识
PubMed 36723414 · DOI 10.1097/CJI.0000000000000450