开发TCR-T细胞疗法,针对异常的HLA-DPB1针对所有原体移植后复发性白血病
Carolyne Barakat1, Yuichiro Inagaki2, Shohei Mizuno3
1Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
International journal of hematology
|June 13, 2023
概括
在全源造血干细胞移植 (HSCT) 后复发性白血病可以被向. 研究人员使用不匹配的人类白细胞抗原 (HLA) -DPB1开发了T细胞疗法,以对抗HSCT后白血病复发.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 移植科学 移植科学
背景情况:
- 复发性白血病后异质造血干细胞移植 (allo-HSCT) 是死亡的主要原因.
- 人类白细胞抗原 (HLA) -DPB1不匹配在无关的allo-HSCT中很常见,并呈现出治疗标.
- 对不匹配的HLA-DPB1进行调配的捐赠者衍生全活性T细胞为移植后白血病复发提供了潜在的策略.
研究的目的:
- 建立和表征特异性T细胞克隆,特定于不匹配的HLA-DPB1等位基因.
- 为了在体外评估这些T细胞克隆的抗白血病活性.
- 探索采用HLA-DPB1特异性T细胞的采用免疫疗法的可行性.
主要方法:
- 隔离HLA-DPB1受限制的T细胞克隆从患者后合并-HSCT.
- 在体外使用白血病细胞系和初级细胞爆发的功能测试.
- 分析T细胞受体 (TCR) 的特异性和抗白血病活性.
- 将克隆TCRcDNA的基因转移到T细胞中.
主要成果:
- 一些受HLA-DPB1限制的T细胞克隆成功建立 (DPB1*02:01, -DPB1*04:02, -DPB1*09:01).
- DPB1*09:01受限制的克隆2A9对多种白血病细胞系和原发性髓性白血病突变,包括具有低HLA-DP表达的细胞系表现出反应性.
- 从克隆 2A9 中介的 HLA-DPB1*09:01 中衍生的TCR工程T细胞在体外受限识别和溶解白血病细胞.
结论:
- 从后合-HSCT全活性CD4+T细胞中诱导不匹配的HLA-DPB1特异性T细胞克隆是可以实现的.
- 克隆的TCRcDNA的基因转移提供了用于采用免疫治疗的T细胞重定向的方法.
- 这些发现支持了针对HLA-DPB1的T细胞治疗在alo-HSCT后治疗复发性白血病的潜力.
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