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
英文原题:The Emerging Role of CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma.
The Emerging Role of CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma.
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霍奇金淋巴瘤(HL)的治疗自19世纪首次描述以来已经发生了巨大的演变,如今许多患者通过一线治疗即可治愈。尽管取得了这些进展,仍有超过10%的患者在初始治疗后出现疾病进展,复发的比例更高。直到最近,除了高强度化疗联合干细胞挽救治疗外,复发和/或难治性HL的治疗选择一直有限。对HL病理生理学理解的深入,加上更具靶向性的治疗方法的出现,重塑了我们对复发/难治性HL治疗及其预后的看法。由此,免疫疗法越来越受到关注,其能够重编程免疫系统以更好地克服HL中存在的免疫抑制微环境,从而增强对癌细胞的杀伤。特别是,嵌合抗原受体(CAR)T细胞正在成为该领域一种有价值的治疗工具。在针对CD30的抗体-药物偶联物取得成功的基础上,经工程化改造以识别相同抗原的CAR-T 细胞现已进入患者治疗。尽管仍处于起步阶段,CAR-T 疗法用于复发/难治性HL在早期临床试验中已展现出非凡的前景,即使在既往经过多线治疗进展的患者中也有望实现持久缓解。本文将综述目前关于CAR-T 细胞用于HL的数据、优化其疗效的策略,以及该疗法未来如何融入HL的治疗范式。
Treatment for Hodgkin lymphoma (HL) has evolved considerably from the time it was originally described in the 19th century with many patients now being cured with frontline therapy. Despite these advances, upwards of 10% of patients experience progressive disease after initial therapy with an even higher percentage relapsing. Until recently there had been limited therapeutic options for relapsed and/or refractory HL outside of highly intensive chemotherapy with stem cell rescue. Improved understanding of the pathophysiology of HL, coupled with the emergence of more targeted therapeutics, has reshaped how we view the treatment of relapsed/refractory HL and its prognosis.
With this, there has been an increased focus on immunotherapies that can reprogram the immune system to better overcome the immunosuppressive milieu found in HL for improved cancer cell killing. In particular, chimeric antigen receptor (CAR) T cells are emerging as a valuable therapeutic tool in this area.
Building on the success of antibody-drug conjugates directed against CD30, CAR T cells engineered to recognize the same antigen are now reaching patients. Though still in its infancy, CAR T therapy for relapsed/refractory HL has shown exceptional promise in early-stage clinical trials with the potential for durable responses even in patients who had progressed through multiple lines of prior therapy.
Here we will review currently available data on the use of CAR T cells in HL, strategies to optimize their effectiveness, and how this therapy may fit into the treatment paradigm of HL going forward.
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