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
携带突变 Fc 间隔区的 Hu8F4-CAR-T 细胞提高靶点特异性并在体内介导抗白血病活性
英文原题：Hu8F4-CAR T cells with mutated Fc spacer segment improve target specificity and mediate anti-leukemia activity in vivo.
查看英文原题
Hu8F4-CAR T cells with mutated Fc spacer segment improve target specificity and mediate anti-leukemia activity in vivo.
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研究概要
在此，我们证明对基于 IgG1 的间隔区进行改造可消除 Fc 受体结合诱导的不良反应，且 Hu8F4-CAR(PQ)-T 细胞可在体内杀伤白血病。
中文摘要
Hu8F4是一种高亲和力T细胞受体样抗体，可识别白血病相关抗原PR1/HLA-A2表位。其CAR形式Hu8F4-CAR包含单链可变片段、人IgG1 CH2CH3胞外间隔区、人CD28共刺激域及人CD3信号域。既往研究显示其体外可高效杀伤表达PR1/HLA-A2的细胞系和AML患者白血病原始细胞；修改IgG间隔区Fc结构域可避免激活诱导的细胞死亡及Fc受体介导脱靶杀伤。本研究构建在CH2域Fc受体结合位点突变的Hu8F4-CAR(PQ)，以防止体内与表达Fcγ受体细胞发生非预期相互作用。转导该CAR的原代人T细胞可特异杀伤体外HLA-A2阳性、PR1阳性白血病细胞；成人供者和脐带血来源的细胞均能在NSG小鼠中清除U937白血病细胞。结果表明改造IgG1间隔区可消除Fc受体结合相关不良效应，Hu8F4-CAR(PQ)-T细胞可在体内杀伤白血病。
展开英文摘要原文
METHODS
We generated Hu8F4-CAR(PQ) with mutated Fc receptor binding sites on the CH2 domain of Hu8F4-CAR to prevent unwanted interactions with Fc gamma receptor-expressing cells in vivo.
RESULTS
The primary human T cells transduced with Hu8F4-CAR(PQ) can specifically lyse HLA-A2 + PR1-expressing leukemia cell lines in vitro. Furthermore, both adult donor-derived and cord blood-derived Hu8F4-CAR(PQ)-T cells are active and can eliminate U937 leukemia cells in NSG mice.
CONCLUSIONS
Herein, we demonstrate that modification of the IgG1-based spacer can eliminate Fc receptor binding-induced adverse effects and Hu8F4-CAR(PQ)-T cells can kill leukemia in vivo.
论文信息
- 作者
- He H、Vedia RA、Lu S、Li Q、Cox KR、St John L、Sergeeva A、Clise-Dwyer K
- 第一作者单位
- Department of Hematopoietic Biology and Malignancy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.United States
- 通讯作者单位
- Department of Hematopoietic Biology and Malignancy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. Electronic address: jmolldre@mdanderson.org.United States
- 文献类型
- 美国 NIH 资助研究
- 期刊
- Cytotherapy2024 Nov
- 原文标识
- PubMed 39033444 · DOI 10.1016/j.jcyt.2024.06.010
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