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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Top advances in lymphoma for 2021.
Top advances in lymphoma for 2021.
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2021年,嵌合抗原受体(CAR)T细胞治疗、抗体偶联药物、双特异性T细胞重定向药物,以及靶向持续性B细胞受体信号的药物,改变了三种最常见淋巴瘤的治疗格局。对于弥漫性大B细胞淋巴瘤,POLARIX研究显示,在一线利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)标准方案基础上改进治疗可带来获益;尽管过去20年付出巨大努力,此前一直未能实现这一突破。在复发难治阶段,两种独特CAR-T 产品已将自体移植推迟至三线治疗,使化疗耐药患者能够更早接受获批疗法。CAR-T 产品过去主要用于侵袭性淋巴瘤,如今也在惰性淋巴瘤中显示出较高缓解率和持久活性。针对惰性淋巴瘤开展的mosunetuzumab研究,为接受过多线细胞毒性药物治疗的患者提供了另一种选择。基于这些趋势,PI3K抑制剂正逐渐被更安全、疗效更持久的疗法取代。
此外,过去一年中,zanubrutinib获批并用于边缘区淋巴瘤,填补了后线治疗需求,尤其适用于体能较差和老年患者。
Chimeric antigen receptor (CAR) T-cell therapy, antibody-drug conjugates, bispecific T-cell redirectors, and agents targeting tonic B-cell receptor signaling have altered the paradigm for three of the most common lymphomas in the year 2021. For diffuse large B-cell lymphoma, the POLARIX study has shown improvement on the standard backbone of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in the frontline setting, a feat that had not been achieved despite great efforts over the past 20 years.
In the relapsed and refractory setting, two unique CAR T-cell products have displaced autologous transplantation to the third line, and they allow patients with chemotherapy-resistant disease to receive approved therapy earlier. CAR T-cell products, once used exclusively in the aggressive lymphoma arena, are now showing high response rates and durable activity against indolent lymphomas.
The investigation of mosunetuzumab in indolent lymphomas offers another option for patients who have received multiple lines of cytotoxic drugs. On the basis of these trends, PI3K inhibitors are being displaced in favor of safer and more durable constructs.
In addition, within the past year, the approval and implementation of zanubrutinib for marginal zone lymphoma have filled a need for later line therapy, especially for less fit and elderly patients.
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