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:CAR T-cell therapy for B-cell lymphoma.
CAR T-cell therapy for B-cell lymphoma.
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靶向CD19的嵌合抗原受体修饰T细胞(CAR-T)疗法彻底改变了复发/难治性B细胞淋巴瘤的治疗。鉴于高危B细胞淋巴瘤患者获得前所未有的缓解率且应答持久,抗CD19 CAR-T 疗法迅速获得美国食品药品监督管理局(FDA)批准,用于多种淋巴瘤亚型。目前,对于接受两线或以上治疗后复发或难治的侵袭性非霍奇金淋巴瘤(NHL)患者,抗CD19 CAR-T 疗法已被视为标准治疗。已有三种第二代抗CD19 CAR-T 产品获FDA批准用于复发/难治性侵袭性B细胞淋巴瘤,套细胞淋巴瘤和滤泡性淋巴瘤适应证也已获批。这使NHL患者能够广泛接受CAR-T 治疗,新的真实世界研究也证实CAR-T 疗法可用于更广泛的患者群体。随着CAR-T 疗法出现,可能会形成一类既往接受过抗CD19 CAR-T 治疗的患者。因而需要研究CAR-T 治疗失败机制,并开展临床试验评估应对策略。本文全面综述FDA批准的抗CD19 CAR-T 产品——axicabtagene ciloleucel、tisagenlecleucel和lisocabtagene maraleucel——在惰性或侵袭性B细胞淋巴瘤患者中的应用,并介绍CAR-T 疗法的失败机制以及正在研究的潜在应对方法。
Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on unprecedented response rates and durability of response in high risk B-cell lymphoma patients, anti-CD19 CAR T-cell therapy was rapidly approved by the FDA for a variety of lymphoma subtypes. Anti-CD19 CAR T-cell therapy is now considered standard of care for patients with relapsed or refractory (R/R) aggressive non-Hodgkin's Lymphoma (NHL) after 2 or more lines of therapy.
Three second-generation anti-CD19 CAR T-cell products have been FDA approved for R/R aggressive B-cell lymphoma and FDA approval has been obtained for Mantle Cell Lymphoma and Follicular lymphoma as well. This has ensured broad access to CAR T-cell therapy for patients with NHL and new real-world trials have helped confirm feasibility of CAR T-cell therapy for a broad patient population.
The emergence of CAR T-cell therapy will likely provide a new patient population who is status post anti-CD19 CAR T-cell therapy. Investigation of mechanisms of failure of CAR T-cell therapy and clinical trials to study strategies to address this are thus required.
Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation to address this.
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