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
一种新型学术型 BCMA-CART（HBI0101）治疗复发/难治性 AL 淀粉样变性的可行性
英文原题：Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis.
查看英文原题
Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis.
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研究概要
BCMA-CART 细胞提供了首个概念验证，表明该疗法对于治疗晚期、RR AL 患者足够安全且高度有效。
研究思路结论见上方概要
目的
AL 淀粉样变性（AL）的治疗通常基于多发性骨髓瘤的治疗方案。抗 B 细胞成熟抗原（BCMA）CAR-T（CAR-T）细胞疗法已获批用于多发性骨髓瘤，但对 AL 患者可能毒性过大。
方法
在此，我们描述了一种新型内部学术型抗BCMA CAR构建体在AL原代细胞上的离体适用性，以及在I期临床试验（NCT04720313）中治疗4例复发/难治性（RR）原发性AL患者的安全性和有效性。
结果
入组时有3例存在MAYO IIIa期心脏受累。治疗相对安全，2例出现短暂且可控的3级细胞因子释放综合征，无任何神经毒性。2例出现的心脏失代偿也短暂且可控。所有患者均观察到总体血液学缓解和完全缓解，4例均出现器官缓解。在中位随访5.2（2.5-9.5）个月内，4例患者均维持缓解。
展开英文摘要原文
PURPOSE
AL amyloidosis (AL) treatments are generally based on those employed for multiple myeloma. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CART)-cell therapy, already approved for multiple myeloma, might be too toxic for patients with AL. EXPERIMENTAL DESIGN: Here we describe the ex vivo applicability of a novel in-house, academic anti-BCMA CAR construct on AL primary cells, as well as the safety and efficacy in 4 patients with relapsed/refractory (RR) primary AL, treated in a phase I clinical trial (NCT04720313).
RESULTS
Three had MAYO stage IIIa cardiac involvement at enrollment. The treatment proved relatively safe, with a short and manageable grade 3 cytokine release syndrome evident in 2 patients and no neurotoxicity in any. Cardiac decompensations, observed in 2 patients, were also short and manageable. The overall hematologic response and complete response rates were observed in all patients with an organ response evident in all four. Within a median follow-up period of 5.2 (2.5-9.5) months, all 4 patients maintained their responses.
CONCLUSIONS
BCMA-CART cells provide a first proof-of-concept that this therapy is safe enough and highly efficacious for the treatment of patients with advanced, RR AL.
论文信息
- 作者
- Kfir-Erenfeld S、Asherie N、Grisariu S、Avni B、Zimran E、Assayag M、Sharon TD、Pick M
- 第一作者单位
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.Israel
- 通讯作者单位
- Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.Israel
- 文献类型
- I 期临床试验 · 非美国政府资助研究
- 期刊
- Clinical cancer research : an official journal of the American Association for Cancer Research2022 Dec 1
- 原文标识
- PubMed 36107221 · DOI 10.1158/1078-0432.CCR-22-0637