CD19-CD28:一种亲和度优化的CD28激动剂,可与格洛菲他马布 (CD20-TCB) 结合使用,作为现成的免疫疗法
Johannes Sam1, Thomas Hofer1, Christine Kuettel1
1Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Schlieren, Switzerland.
Blood
|March 4, 2024
概括
一种新的双特异性CD19向的CD28激动剂,RG6333,在与T细胞双特异性抗体 (如glofitamab) 结合时,可以增强T细胞的反应. 这种组合疗法有望通过促进T细胞介导的瘤细胞杀死来改善淋巴瘤治疗.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物技术是生物技术.
背景情况:
- 有效的T细胞反应需要T细胞受体 (TCR) 参与 (信号1) 和共刺激信号 (信号2).
- 像glofitamab这样的T细胞双特异性抗体 (TCB) 通过激活CD3ε和瘤抗原提供信号1,在CD20表达性淋巴瘤中显示出有效性.
- 增强T细胞共刺激可能会加深和延长T细胞介导的瘤细胞杀死.
研究的目的:
- 开发和评估一种双特异性CD19向的CD28激动剂 (CD19-CD28),RG6333,作为一种增强TCB疗效的组合疗法.
- 评估RG6333与glofitamab结合治疗侵袭性淋巴瘤的安全性和有效性.
- 调查RG6333与其他辅助刺激激动剂结合的潜力.
主要方法:
- 开发RG6333,一种针对CD19的CD28激动剂,具有针对选择性活动的工程特征.
- 使用患者衍生的外周血液单核细胞和脏样本进行ex vivo测定,以评估T细胞效应器功能.
- 在体内研究使用具有侵略性淋巴瘤的人性化小鼠来评估瘤回归和长期控制.
主要成果:
- 在ex vivo测定中,RG6333增强了T细胞效应因子功能,当与glofitamab结合使用时.
- 格罗菲他马布和RG6333的组合促进了人性化小鼠中侵略性淋巴瘤的回归.
- 包括glofitamab,RG6333和4-1BB激动剂 (CD19-4-1BBL) 在内的三重组合,与双重组合或glofitamab单独治疗相比,显示出优异的长期瘤控制.
结论:
- RG6333是格洛菲他马布和类似的TCB的安全有效的组合伙伴,增强T细胞介导的抗瘤活性.
- 工程 CD19-CD28 激动剂提供了一个有前途的策略,以改善淋巴瘤治疗的结果.
- 目前,RG6333正在一期临床试验 (NCT05219513) 中与glofitamab.com结合进行研究.
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