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
CD4⁺ CAR-T 细胞强劲扩增与 Ciltacabtagene Autoleucel 治疗后非 ICANS 神经毒性相关
英文原题：Robust CD4(+) CAR T cell Expansion Is Associated with Non-ICANS Neurotoxicities Following Ciltacabtagene Autoleucel.
查看英文原题
Robust CD4(+) CAR T cell Expansion Is Associated with Non-ICANS Neurotoxicities Following Ciltacabtagene Autoleucel.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
非 ICANS 神经毒性（NINTs）是与 ciltacabtagene autoleucel 相关的严重、非典型毒性，ciltacabtagene autoleucel 是一种获批用于复发/难治性多发性骨髓瘤的商业化嵌合抗原受体（CAR）T 细胞疗法。导致 NINTs 发生的危险因素目前了解甚少。在一个 109 例患者的队列中，我们确定了易感危险因素，并提出减轻 NINTs 的策略。
我们发现，高峰值绝对淋巴细胞计数是 NINT 的强预测因子，其与基于流式细胞术的外周血 CAR-T 细胞定量直接相关。观察到的 CAR 淋巴细胞增多为多克隆，并偏向于富含记忆标志物表达的 CD4 + CAR-T 细胞。随后，我们鉴定了与 CAR 淋巴细胞增多相关的 CD4 + CAR-T 细胞群体，这些群体表现出炎症通路基因表达增加。
最后，我们描述了与 NINT 相关的 CD4 + CAR-T 细胞群体，这些群体是未来探索的潜在治疗靶点。
展开英文摘要原文
Non-ICANS neurotoxicities (NINTs) are serious, atypical toxicities associated with ciltacabtagene autoleucel, a commercial chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory multiple myeloma. Risk factors contributing to the development of NINTs are poorly understood. In a cohort of 109 patients, we identify predisposing risk factors and propose strategies to mitigate NINTs.
We show that high peak absolute lymphocyte count is a strong NINT predictor which directly correlates with flow cytometry-based peripheral blood CAR T cell quantitation. The observed CAR lymphocytosis was polyclonal with a bias towards CD4 + CAR T cells rich in memory marker expression.
We then identified CAR lymphocytosis associated CD4 + CAR T cell populations which exhibited increased inflammatory pathway gene expression.
Finally, we characterize NINT associated CD4 + CAR T cell populations which are potential therapeutic targets for future exploration.
论文信息
- 作者
- Jurgens EM、Mitra S、Herrera K、Nemirovsky D、Bready B、Derkach A、Hosszu K、McAvoy D
- 第一作者单位
- Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; New York, NY, USA.United States
- 通讯作者单位
- Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center; New York, NY, USA.United States
- 文献类型
- 预印本
- 期刊
- medRxiv : the preprint server for health sciences2025 Oct 30
- 原文标识
- PubMed 41282927 · DOI 10.1101/2025.10.28.25338924