特定于CD22的T细胞受体使B细胞恶性瘤的有效采用T细胞疗法成为可能
Simone Rhein1, Neşe Çakmak-Görür1, Corinna Grunert1
1Charité-Universitätsmedizin Berlin, Berlin, Germany.
Blood
|October 16, 2025
概括
CD19 CAR-T疗法面临着CD19低瘤复发的挑战. 新的CD22T细胞受体 (TCR) 疗法对这些抗性B细胞恶性瘤具有更高的疗效,提供了一个有前途的替代方案.
科学领域:
- 免疫治疗是一种免疫疗法.
- 在瘤学瘤学.
- 细胞疗法细胞疗法
背景情况:
- CD19仿真抗原受体 (CAR) T细胞疗法是B细胞恶性瘤的标准,但由于CD19低/负克隆而复发.
- 双特异性CD19/CD22CAR-T细胞由于抗原下调和持久性差,其疗效有限.
- CD22在B细胞淋巴瘤和白血病中无处不在表达,使其成为一个可行的免疫治疗点.
研究的目的:
- 为了评估T细胞受体 (TCR) 的疗效,工程T细胞向CD22.
- 在临床前模型中,将CD22 TCR-T细胞与CD19 CAR-T细胞和CD22 CAR-T细胞进行比较.
- 评估CD22 TCR-T细胞在CD19治疗后复发性B细胞恶性瘤治疗中的潜力.
主要方法:
- 使用人性化的小鼠模型识别一种高亲和度的CD22特异性TCR,针对由HLA-A*02:01呈现的CD22表位.
- 在实验室中评估CD22 TCR-T细胞特异性和针对CD22阳性细胞系和患者衍生瘤样本的疗效.
- 在Nalm6 B细胞白血病模型中对CD22 TCR-T细胞活性进行体内验证,并与CD22 CAR-T细胞进行比较.
主要成果:
- 在体外,CD22 TCR-T细胞表现出高特异性和有效性.
- CD22 TCR-T细胞在识别CD22低瘤细胞 (包括对CD19 T细胞疗法耐药的瘤细胞) 中优于CD22 CAR-T细胞.
- CD22 TCR-T细胞有效地向表达细胞内CD22的瘤细胞,与CD22 CAR-T细胞不同.
- 活体内研究证实了CD22 TCR-T细胞对CD22低B细胞白血病的优越活性.
结论:
- 基于CD22 TCR的疗法是CD22低B细胞恶性瘤的有效治疗选择.
- 这种方法对CD19 CAR-T治疗后复发的患者有希望.
- CD22 TCR-T细胞在B细胞癌症中提供了一种有效的策略来对抗抗原逃逸机制.
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