鉴定和表征具有高亲和度和强烈抗白血病活性的血管活性肠道受体对手
bioRxiv : the preprint server for biology
|November 28, 2024
概括
新的VIP受体对抗剂增强T细胞激活和抗白血病活性. 这些新型化合物显示为急性髓性白血病的免疫疗法,特别是复发病例的承诺.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 血管活性肠 (VIP) 影响瘤生长和免疫反应.
- 维普抗剂 (VIPhyb) 已经显示出增强T细胞激活和抗白血病活性的潜力.
研究的目的:
- 通过修改VIPhyb C-终端序列来开发更强大的VIP受体 (VIP-R) 抗剂.
- 改善VIP-R结合亲和力和血稳定性,以提高治疗效果.
主要方法:
- VIPhyb变体的组合库合成.
- 在人体VIP受体 (VPAC1,VPAC2) 预测结合亲和力的选.
- 在小鼠模型中体外测试T细胞激活和体内抗白血病活性.
主要成果:
- 合成和测试了15种VIP-R对手.
- 高预测的结合亲和力与增强的T细胞增殖和抗白血病活性正相关.
- ANT308和ANT195在体外和体内表现出强大的疗效,ANT308降低了CREB酸化并增强了AML患者T细胞中的细胞毒性标记物.
结论:
- 在模型与体外和体内数据相结合,确定了有前途的VIP-R对抗剂候选者.
- ANT308和ANT195代表了急性髓性白血病 (AML) 的潜在新型免疫疗法.
- 这些抗体可能对复发性AML的患者特别有益.
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