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
长期双特异性抗体暴露后反复 CAR-T 细胞制备失败相关的 T 细胞功能障碍：一例病例报告
英文原题：T cell dysfunction associated with repeated CAR-T cell manufacturing failure following prolonged bispecific antibody exposure: a case report.
查看英文原题
T cell dysfunction associated with repeated CAR-T cell manufacturing failure following prolonged bispecific antibody exposure: a case report.
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研究概要
这些发现将严重的T细胞功能障碍与反复的CAR-T 细胞制备失败联系起来，并提示采血前免疫表型分析可能识别出存在制备失败风险的患者。
研究思路结论见上方概要
背景
CAR-T 细胞治疗和双特异性抗体（BsAb）已显著改善复发/难治性多发性骨髓瘤（r/rMM）的结局，但最佳治疗顺序仍不明确，尤其是既往 BsAb 暴露对后续 CAR-T 可生产性的影响。病例报告：一名 72 岁 r/rMM 男性患者在接受包括 FcRL5 × CD3 双特异性抗体在内的多种治疗后，发生了两次 CAR-T 细胞生产失败事件。两次采集均未能获得足够的 CAR-T 细胞剂量。纵向免疫表型分析显示 T 细胞功能障碍标志物，包括 CCR7、CD27 和 CD28 缺失，同时 TCR 驱动的增殖严重受损，而白细胞介素-2 反应性保留。
展开英文摘要原文
BACKGROUND
CAR-T cell therapy and bispecific antibodies (BsAb) have significantly improved outcomes in relapsed/refractory multiple myeloma (r/rMM), yet the optimal treatment sequence remains unclear, particularly regarding the impact of prior BsAb exposure on downstream CAR-T manufacturability. CASE PRESENTATION: A 72-year-old man with r/rMM had two CAR-T cell manufacturing failure events following multiple therapies including an FcRL5 × CD3 bispecific antibody. Both collections yielded an insufficient CAR-T cell dose. Longitudinal immune phenotyping revealed markers of T cell dysfunction, including loss of CCR7, CD27, and CD28, alongside severely impaired TCR-driven proliferation with preserved interleukin-2 responsiveness.
CONCLUSION
These findings link profound T cell dysfunction with repeated CAR-T cell manufacturing failures and suggest that pre-leukapheresis immune phenotyping may identify patients at risk for manufacturing failure.
论文信息
- 作者
- Henry SJW、Pfeffer K、Shim KG、Meermeier EW、Feng F、Wiedmeier JE、Chhabra S、Bergsagel PL
- 单位
- Department of Laboratory Medicine and Pathology, Mayo Clinic in Arizona, Phoenix, AZ, USA.United States
- 文献类型
- 病例报告
- 期刊
- Leukemia research reports2026
- 原文标识
- PubMed 42831193 · DOI 10.1016/j.lrr.2026.100611
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