Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
Faculty of Pharmacy, Department Pharmacology, Bahauddin Zakariya University, Multan, Pakistan.
Am J Physiol Gastrointest Liver Physiol. 2020 Jun 1;318(6):G1055-G1069. doi: 10.1152/ajpgi.00068.2020. Epub 2020 May 4.
Liver cancer is a worldwide disease, and, currently, due to the poor prognostic and therapeutic options of liver cancer, we investigated the T cell epitopes as potential therapeutic vaccine candidates to get the benefit of experimental processes and utilize the complete ability of the immune system compared with other artificial ex vivo proliferation of T cells. Activation of T cells targets and kills several tumors, developing a strong rationale for the improvement of immunotherapeutic strategies to cancer therapy. To predict T cell epitopes for liver cancer, we designed a comprehensive immunoinformatics framework involving data mining, immunogenicity prediction, functional proteomic analysis, conservation studies, molecular modeling, and in vivo validation analysis. We found the binding affinity of antigenic peptides with major histocompatibility complex (MHC) I molecules to control the cancerous activity. Five extracellular antigenic proteins, including complement protein (C6), serotransferrin, coagulation factor XIII B, serum albumin (ALB), and prothrombin, were identified. We predicted and synthesized T cell epitopes to human leukocytes antigen-A*01:01 allele of MHC class I molecule. The hematological assay and IgG ELISA showed that C6 and ALB epitopes induced the production of lymphocytes, granulocytes, and peptide-specific IgG in immunized rats. We observed substantial high levels of granzymes B in serum samples of C6 and ALB compared with control, indicating the activity of cytotoxic T cells. We concluded that C6 and ALB are likely to contain potential epitopes for the induction of protective effector molecules, supporting the feasibility of therapeutic peptide-based vaccine for liver cancer. We observed substantial high levels of granzymes B in serum samples of component C6 (C6) and albumin (ALB) compared with control, indicating the activity of cytotoxic T cells. We concluded that C6 and ALB are likely to contain potential epitopes for the induction of protective effector molecules, supporting the feasibility of therapeutic peptide-based vaccine for liver cancer.
肝癌是一种全球性疾病，目前由于肝癌的预后和治疗选择不佳，我们研究了 T 细胞表位作为潜在的治疗性疫苗候选物，以利用实验过程并利用免疫系统的全部能力，与其他体外人工扩增的 T 细胞相比。T 细胞的激活靶向并杀死多种肿瘤，为癌症治疗的免疫治疗策略的改进提供了强有力的依据。为了预测肝癌的 T 细胞表位，我们设计了一个综合的免疫信息学框架，包括数据挖掘、免疫原性预测、功能蛋白质组学分析、保守性研究、分子建模和体内验证分析。我们发现抗原肽与主要组织相容性复合物（MHC）I 分子的结合亲和力可控制癌变活性。鉴定了五种细胞外抗原蛋白，包括补体蛋白（C6）、转铁蛋白、凝血因子 XIII B、血清白蛋白（ALB）和凝血酶原。我们预测并合成了与人类白细胞抗原-A*01:01 等位基因 MHC Ⅰ类分子结合的 T 细胞表位。血液学检测和 IgG ELISA 显示，C6 和 ALB 表位在免疫大鼠中诱导淋巴细胞、粒细胞和肽特异性 IgG 的产生。与对照相比，我们在 C6 和 ALB 的血清样本中观察到大量高水平的颗粒酶 B，表明细胞毒性 T 细胞的活性。我们得出结论，C6 和 ALB 可能含有诱导保护性效应分子的潜在表位，支持基于治疗性肽的肝癌疫苗的可行性。与对照相比，我们在 C6（C6）和白蛋白（ALB）的血清样本中观察到大量高水平的颗粒酶 B，表明细胞毒性 T 细胞的活性。我们得出结论，C6 和 ALB 可能含有诱导保护性效应分子的潜在表位，支持基于治疗性肽的肝癌疫苗的可行性。
