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
靶向克隆性 TCRVβ 链的 CAR-iNKT 细胞作为治疗 T 细胞淋巴瘤的精准策略
英文原题：CAR-iNKT cells targeting clonal TCRVβ chains as a precise strategy to treat T cell lymphoma.
查看英文原题
CAR-iNKT cells targeting clonal TCRVβ chains as a precise strategy to treat T cell lymphoma.
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研究概要
因此，我们为抗 TCRV CAR-T 和 iNKT 细胞疗法有效且选择性治疗 TCL 提供了概念验证，后者提供了“现货型”免疫治疗的选择。
中文摘要
方法
作为概念验证，我们构建了靶向4种TCR V亚基的CAR。以常规T细胞作为效应细胞（CAR-T）检测CAR构建体的疗效。由于恒定型NKT（iNKT）细胞不会引发急性移植物抗宿主病，适合用于“现货型”免疫疗法，我们进一步制备了抗TCR V CAR-iNKT细胞。
结果
抗TCR V CAR-T 细胞可选择性杀伤相应肿瘤靶细胞，同时保留超过90%的生理性TCR库。CAR-iNKT细胞在体内抑制TCL生长，对成人T细胞白血病/淋巴瘤患者的恶性细胞也具有选择性活性，且不会激活HTLV-1表达。讨论：因此，本研究证实，靶向TCR V的CAR-T 和CAR-iNKT细胞疗法可有效且选择性地治疗TCL；后者还可提供“现货型”免疫疗法选择。
展开英文摘要原文
METHODS
As proof of concept, we generated CAR constructs to target four TCRV subunits. Efficacy of the CAR constructs was tested using conventional T cells as effectors (CAR-T). Since invariant NKT (iNKT) cell do not incite acute graft-versus-host disease and are suitable for 'off-the-shelf' immunotherapy, we generated anti-TCRV CAR-iNKT cells.
RESULTS
We show that anti-TCRV CAR-T cells selectively kill their cognate tumour targets while leaving >90% of the physiological TCR repertoire intact. CAR-iNKT cells inhibited the growth of TCL in vivo , and were also selectively active against malignant cells from Adult T cell leukaemia/lymphoma patients without activating expression of HTLV-1. DISCUSSION: Thus we provide proof-of-concept for effective and selective anti-TCRV CAR-T and -iNKT cell-based therapy of TCL with the latter providing the option for 'off-the-shelf' immunotherapy.
论文信息
- 作者
- Rowan AG、Ponnusamy K、Ren H、Taylor GP、Cook LBM、Karadimitris A
- 第一作者单位
- Section of Virology, Department of Infectious Disease, Imperial College London, London, United Kingdom.United Kingdom
- 通讯作者单位
- Hugh and Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.United Kingdom
- 文献类型
- 非美国政府资助研究
- 期刊
- Frontiers in immunology2023
- 原文标识
- PubMed 36936927 · DOI 10.3389/fimmu.2023.1118681
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