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通过多组学分析和噬菌体-真核细胞相互作用构建个体化癌症治疗策略。

Building Personalized Cancer Therapeutics through Multi-Omics Assays and Bacteriophage-Eukaryotic Cell Interactions.

机构信息

Complete Omics Inc., 1448 S. Rolling Rd, Baltimore, MD 21227, USA.

出版信息

Int J Mol Sci. 2021 Sep 8;22(18):9712. doi: 10.3390/ijms22189712.

Abstract

Bacteriophage-eukaryotic cell interaction provides the biological foundation of Phage Display technology, which has been widely adopted in studies involving protein-protein and protein-peptide interactions, and it provides a direct link between the proteins and the DNA encoding them. Phage display has also facilitated the development of new therapeutic agents targeting personalized cancer mutations. Proteins encoded by mutant genes in cancers can be processed and presented on the tumor cell surface by human leukocyte antigen (HLA) molecules, and such mutant peptides are called Neoantigens. Neoantigens are naturally existing tumor markers presented on the cell surface. In clinical settings, the T-cell recognition of neoantigens is the foundation of cancer immunotherapeutics. This year, we utilized phage display to successfully develop the 1st antibody-based neoantigen targeting approach for next-generation personalized cancer therapeutics. In this article, we discussed the strategies for identifying neoantigens, followed by using phage display to create personalized cancer therapeutics-a complete pipeline for personalized cancer treatment.

摘要

噬菌体-真核细胞相互作用为噬菌体展示技术提供了生物学基础,该技术已广泛应用于蛋白质-蛋白质和蛋白质-肽相互作用的研究中,并为蛋白质与其编码 DNA 之间建立了直接联系。噬菌体展示技术还促进了针对个性化癌症突变的新型治疗药物的开发。癌症中突变基因编码的蛋白质可以通过人类白细胞抗原(HLA)分子在肿瘤细胞表面进行加工和呈递,此类突变肽被称为新抗原。新抗原是存在于细胞表面的天然肿瘤标志物。在临床环境中,T 细胞对新抗原的识别是癌症免疫疗法的基础。今年,我们成功地利用噬菌体展示技术开发了针对下一代个性化癌症治疗的首个基于抗体的新型抗原靶向方法。本文讨论了鉴定新抗原的策略,然后使用噬菌体展示技术创建个性化癌症治疗方法——即完整的个性化癌症治疗流水线。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b850/8468737/1713231025af/ijms-22-09712-g001.jpg

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