Preparation and Evaluation of a Multi-Epitope Peptide for Assessing Immunotherapy of Colorectal Cancer in Vivo

IF 1.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fatemeh Bahramibanan, Meysam Soleimani, Amir Taherkhani, Hamidreza Ghadimipour, Rezvan Najafi, Nastaran Barati, Katayoun Derakhshandeh
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Abstract

The presence of tumor heterogeneity is a critical issue that restricts the success of targeted therapies and negatively impacts patient outcomes. Recent studies have concentrated on the development of multi-epitope peptides that exhibit considerable overexpression in cancerous tissues with the aim of activating immune cells and utilizing immune-mediated responses to effectively suppress tumor growth. In this study, genes with increased expression in colorectal cancer (CRC) were identified using GEO data and R software. Following overexpression confirmation of APCDD1, we identified epitopes from the protein that can be recognized by various MHC molecules and presented on APC cell surfaces. Subsequent to expression and purification of the multi-epitope peptide and investigation on the BALB/c mice harboring tumor xenograft, obtained results showed a significant reduction in tumor growth, mitotic cell count, angiogenesis, metastasis, and an increase in Tumor-Infiltrating Lymphocytes (TILs) in the tumor microenvironment. Overall, the finding highlight the potential of multi-epitope peptide in CRC immunotherapy, where it may address the significant challenge of tumor heterogeneity.

Abstract Image

一种多表位肽的制备及其在体内评价大肠癌免疫治疗效果的研究。
肿瘤异质性的存在是限制靶向治疗成功和对患者预后产生负面影响的关键问题。最近的研究集中在多表位肽的开发上,这些多表位肽在癌组织中表现出相当大的过表达,目的是激活免疫细胞并利用免疫介导反应有效地抑制肿瘤生长。在本研究中,使用GEO数据和R软件鉴定结直肠癌(CRC)中表达增加的基因。在确认APCDD1过表达后,我们从该蛋白中鉴定出可被多种MHC分子识别并呈现在APC细胞表面的表位。通过对多表位肽的表达和纯化,以及对携带肿瘤异种移植物的BALB/c小鼠的研究,获得的结果显示肿瘤生长、有丝分裂细胞计数、血管生成、转移显著减少,肿瘤微环境中肿瘤浸润淋巴细胞(til)增加。总的来说,这一发现突出了多表位肽在结直肠癌免疫治疗中的潜力,它可能解决肿瘤异质性的重大挑战。
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来源期刊
The Protein Journal
The Protein Journal 生物-生化与分子生物学
CiteScore
5.20
自引率
0.00%
发文量
57
审稿时长
12 months
期刊介绍: The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.
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