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利用人工智能蛋白质扩散进行 PD-1 靶向抗体发现。

PD-1 Targeted Antibody Discovery Using AI Protein Diffusion.

机构信息

Tuple LLC, Charlotte, NC, USA.

Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA.

出版信息

Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241275947. doi: 10.1177/15330338241275947.

Abstract

The programmed cell death protein 1 (PD-1, CD279) is an important therapeutic target in many oncological diseases. This checkpoint protein inhibits T lymphocytes from attacking other cells in the body and thus blocking it improves the clearance of tumor cells by the immune system. While there are already multiple FDA-approved anti-PD-1 antibodies, including nivolumab ( from Bristol-Myers Squibb) and pembrolizumab ( from Merck), there are ongoing efforts to discover new and improved checkpoint inhibitor therapeutics. In this study, we present multiple anti-PD-1 antibody fragments that were derived computationally using protein diffusion and evaluated through our scalable, pipeline. Here we present nine synthetic Fv structures that are suitable for further empirical testing of their anti-PD-1 activity due to desirable predicted binding performance.

摘要

程序性细胞死亡蛋白 1(PD-1,CD279)是许多肿瘤疾病中重要的治疗靶点。这种检查点蛋白抑制 T 淋巴细胞攻击体内的其他细胞,因此阻断它可以改善免疫系统清除肿瘤细胞的能力。虽然已经有多种 FDA 批准的抗 PD-1 抗体,包括nivolumab(来自 Bristol-Myers Squibb)和 pembrolizumab(来自 Merck),但仍在努力发现新的和改进的检查点抑制剂治疗方法。在这项研究中,我们使用蛋白质扩散计算得到了多种抗 PD-1 抗体片段,并通过我们的可扩展管道进行了评估。这里我们提出了九个合成 Fv 结构,由于其良好的预测结合性能,适合进一步对其抗 PD-1 活性进行实证测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea4/11375674/adfcf038833e/10.1177_15330338241275947-fig1.jpg

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