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双检查点Aptamer免疫疗法:揭示了针对CTLA-4和NKG2A的定制癌症治疗

Mohamad Ammar Ayass¹, Trivendra Tripathi¹, Natalya Griko¹

¹Ayass Bioscience LLC, 8501 Wade Blvd, Bld 9, Frisco, TX 75034, USA.

|March 13, 2024

概括

这项研究开发了一种新型的阿巴,AYA22T-R2-13,它针对CTLA-4和NKG2A免疫检查点. 这种双重向的阿巴酶增强了T和NK细胞的活性,从而改善了瘤细胞的杀死 in vitro.

科学领域:

免疫治疗是一种免疫疗法.
计算生物学计算生物学
在瘤学瘤学.

背景情况:

免疫疗法,特别是针对CTLA-4和PD-1/PD-L1通路,显示出希望,但在响应率和不良影响方面面临挑战.
抑制性受体的双重向提供了一种潜在的策略,以克服癌症治疗中的这些局限性.

研究的目的:

通过计算设计和验证针对双抑制受体,细胞毒性T-淋巴细胞相关蛋白4 (CTLA-4) 和自然杀手组2A (NKG2A) 的aptamers.
为了增强CD8+T细胞和NK细胞的功能,改善瘤细胞溶解.

主要方法:

在二重受体结合的体体设计和计算分析 (HADDOCK分数).
实验验证使用酶链接免疫吸收试验 (ELISA) 和流细胞计测试以确定结合特异性.
使用乳酸脱酶 (LDH) 细胞毒性试验进行体外功能评估.

主要成果:

亚酶AYA22T-R2-13对CTLA-4和NKG2A受体表现出高的结合亲和力和特异性.
结合性试验证实了CTLA-4和NKG2A在T细胞和NK细胞上的选择性相互作用.
通过AYA22T-R2-13阻断CTLA-4或NKG2A,在体外显著增加了CD8T细胞和NK细胞介导的瘤细胞溶解.

结论:

AYA22T-R2-13对CTLA-4和NKG2A表现出精确的结合,使其成为免疫检查点阻断受体酶研究的有希望的候选人.
胺酶通过释放T和NK细胞来增强抗瘤免疫反应,这表明具有高特异性和低毒性癌症免疫治疗的潜力.

关键词:

在 CTLA-4 中.在NKG2A中,NKG2A是NKG2A.一个aptamer的应用程序.癌症癌症癌症癌症癌症检查站检查站检查站检查站检查站免疫疗法免疫疗法

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