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人结直肠癌治疗干预候选疫苗——细胞表面成纤维细胞激活蛋白-2(Fap2):一种免疫信息学方法

Cell Surface Fibroblast Activation Protein-2 (Fap2) of as a Vaccine Candidate for Therapeutic Intervention of Human Colorectal Cancer: An Immunoinformatics Approach.

作者信息

Padma Somrita, Patra Ritwik, Sen Gupta Parth Sarthi, Panda Saroj Kumar, Rana Malay Kumar, Mukherjee Suprabhat

机构信息

Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol 713340, West Bengal, India.

School of Biosciences & Bioengineering, D. Y. Patil International University, Akurdi, Pune 411044, Maharashtra, India.

出版信息

Vaccines (Basel). 2023 Feb 23;11(3):525. doi: 10.3390/vaccines11030525.

Abstract

Colorectal cancer (CRC) is one of the most common cancers and is the second-highest in cancer-related deaths worldwide. The changes in gut homeostasis and microbial dysbiosis lead to the initiation of the tumorigenesis process. Several pathogenic gram-negative bacteria including are the principal contributors to the induction and pathogenesis of CRC. Thus, inhibiting the growth and survival of these pathogens can be a useful intervention strategy. Fibroblast activation protein-2 (Fap2) is an essential membrane protein of that promotes the adherence of the bacterium to the colon cells, recruitment of immune cells, and induction of tumorigenesis. The present study depicts the design of an in silico vaccine candidate comprising the B-cell and T-cell epitopes of Fap2 for improving cell-mediated and humoral immune responses against CRC. Notably, this vaccine participates in significant protein-protein interactions with human Toll-like receptors, especially with TLR6 reveals, which is most likely to be correlated with its efficacy in eliciting potential immune responses. The immunogenic trait of the designed vaccine was verified by immune simulation approach. The cDNA of the vaccine construct was cloned in silico within the expression vector pET30ax for protein expression. Collectively, the proposed vaccine construct may serve as a promising therapeutic in intervening -induced human CRC.

摘要

结直肠癌(CRC)是最常见的癌症之一,在全球癌症相关死亡中排名第二。肠道稳态的变化和微生物失调导致肿瘤发生过程的启动。包括几种致病性革兰氏阴性菌在内,是CRC诱导和发病机制的主要促成因素。因此,抑制这些病原体的生长和存活可能是一种有用的干预策略。成纤维细胞活化蛋白-2(Fap2)是一种重要的膜蛋白,它促进细菌与结肠细胞的粘附、免疫细胞的募集以及肿瘤发生的诱导。本研究描述了一种基于计算机设计的候选疫苗,该疫苗包含Fap2的B细胞和T细胞表位,用于改善针对CRC的细胞介导免疫和体液免疫反应。值得注意的是,这种疫苗与人类 Toll 样受体存在显著的蛋白质-蛋白质相互作用,尤其是与TLR6的相互作用,这很可能与其引发潜在免疫反应的功效相关。通过免疫模拟方法验证了设计疫苗的免疫原性特征。在计算机上,将疫苗构建体的cDNA克隆到表达载体pET30ax中用于蛋白质表达。总体而言,所提出的疫苗构建体可能是干预诱导的人类CRC的一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0389/10056511/48d39ea5a26c/vaccines-11-00525-g001.jpg

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