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
校准的 CAR 信号使大 B 细胞淋巴瘤低剂量治疗成为可能
英文原题：Calibrated CAR Signaling Enables Low-Dose Therapy in Large B-Cell Lymphoma.
查看英文原题
Calibrated CAR Signaling Enables Low-Dose Therapy in Large B-Cell Lymphoma.
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中文摘要
研究者设计了靶向CD19的CAR，包含经校准的信号模块1XX，与传统CD28/CD3ζ或4-1BB/CD3ζ CAR不同。本文报告19(T2)28z-1XX CAR-T 用于复发/难治性大B细胞淋巴瘤的首次人体I期试验。研究假设该CAR在较低细胞剂量下仍有效，并从较低剂量开始设置4个递增剂量。28例患者总体缓解率为82%、完全缓解率为71%；低剂量组16例分别为88%和75%。中位随访24个月时，1年无事件生存率为61%。3级CRS和神经毒性发生率较低。经校准的1XX CAR效力使低剂量下也有优异疗效，可能有益于其他血液肿瘤、实体瘤及自身免疫病治疗。
展开英文摘要原文
We designed a CD19-targeted CAR comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3z and 4-1BB/CD3z CARs.
Here we report the first-in-human, phase 1 clinical trial of 19(T2)28z-1XX CAR T cells in relapsed/refractory large B-cell lymphoma.
We hypothesized that 1XX CAR T cells may be effective at low doses and investigated 4 doubling dose levels starting from 25 10 6 CAR T cells. The overall response rate (ORR) was 82% and complete response (CR) rate 71% in the entire cohort (n=28) and 88% ORR and 75% CR in 16 patients treated at 25 10 6 . With the median follow-up of 24 months, the 1-year EFS was 61% (95% CI: 45-82%).
Overall, grade 3 CRS and ICANS rates were low at 4% and 7%. The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses and may benefit the treatment of other hematological malignancies, solid tumors and autoimmunity.
论文信息
- 作者
- Park J、Lia Palomba M、Perica K、Devlin S、Shah G、Dahi P、Lin R、Salles G
- 单位
- Memorial Sloan Kettering Cancer Center.
- 文献类型
- 预印本
- 期刊
- Research square2024 Jul 2
- 原文标识
- PubMed 39011120 · DOI 10.21203/rs.3.rs-4619285/v1