Department of Hematology and Medical Oncology.
Department of Pathology, Paracelsus Medical University, Klinikum Nuernberg, Nuremberg, Germany.
J Immunother. 2023;46(2):56-58. doi: 10.1097/CJI.0000000000000450. Epub 2023 Jan 10.
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.
慢性淋巴细胞白血病向侵袭性淋巴瘤的转化，称为里希特转化，常伴有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。一种可能性是使用嵌合抗原受体 T 细胞进行细胞免疫治疗。然而，由于这些患者免疫系统受损，细胞可用的时间延迟和效应细胞数量有限，可能会影响这种方法的疗效。另一种有前途的尝试可能是使用γδ T 细胞治疗。一旦被激活，它们对多种类型的恶性肿瘤表现出多种抗肿瘤作用。此外，它们可以在同种异体环境中安全使用，并已在临床研究中证明可以在体内增殖。此外，体外数据还表明，单克隆抗体可以显著增强γδ T 细胞的细胞毒性。在这里，我们介绍了一位患有里希特转化且对多线免疫化疗均无反应的患者。由于缺乏进一步的治疗选择，我们采用了同种异体单倍体γδ T 细胞过继转移联合单克隆抗体奥滨尤妥珠单抗的个体化治疗。通过这种治疗方法达到了组织学确认的完全缓解，且未观察到相关副作用。该病例强调了 γδ T 细胞的潜力和这种治疗方法在进一步临床试验中的可行性。
