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:Incorporating radiation with anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory non-Hodgkin lymphoma: A multicenter consensus approach.
Incorporating radiation with anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory non-Hodgkin lymphoma: A multicenter consensus approach.
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抗CD19CAR-T 细胞疗法(CAR-T)已彻底改变了复发和/或难治性B细胞非霍奇金淋巴瘤的治疗结局。然而,CAR-T 仍受限于其可及性、毒性和缓解持久性。并非所有患者都能进入CAR-T 输注阶段,部分患者因疾病进展而无法接受治疗。在接受CAR-T 的患者中,相当数量的患者会出现危及生命的细胞因子释放综合征毒性,且不到半数能维持持久缓解,大多数患者在CAR-T 前已存在的病灶部位复发。放射治疗作为一种有前景的围CAR-T 期和挽救性治疗手段,可改善这些患者的结局。证据表明,CAR-T 前的桥接放疗可在制备期间控制疾病、提高缓解率和局部控制率、减少肿瘤负荷/减瘤并降低细胞因子释放综合征的严重程度,并可能延长无病间期和生存期,尤其是在大包块疾病患者中。CAR-T 后残留病灶的巩固性放疗可改变复发模式,改善局部无复发生存期和无进展生存期。对于CAR-T 后复发疾病的挽救性放疗,在局限性复发疾病患者中全面照射可获得良好的生存结局,而对弥漫性复发疾病患者则可缓解症状。围CAR-T 期疾病的生物学机制尚不清楚,需要进一步研究探索放射治疗(RT)的最佳时机和剂量。在本综述中,我们探讨CAR-T 最重大的挑战,回顾并提出RT如何帮助缓解这些挑战,并提供Mayo Clinic专家关于将RT与CAR-T 相结合的方法。
Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma.
However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease.
Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease.
The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.
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