Experimental analysis of T cell epitopes for designing liver cancer vaccine predicted by system-level immunoinformatics approach.

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.NEW & NOTEWORTHY 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.

miRNA in Hepatocellular Carcinoma: Pathogenesis and Therapeutic Approaches.

Hepatocellular carcinoma (HCC) is a worldwide disease. Because therapeutic measures are ineffective, HCC currently has a poor prognosis. The main causes of HCCs are alcoholism, hepatitis, and metabolic syndrome. Normally hygieinic studies revealed that there is lower survival rate of HCC. MicroRNAs (miRNAs) consist of short noncoding sequences of RNA (20 to 24 nucleotides), which posttranscriptionally regulate the expression of the protein coding genes. MicroRNAs have been proposed to be prospective therapeutic molecules and targets. For testing miRNA-based therapies, HCC is a remarkable model because it may be targeted by delivery of oligonucleotides. Current studies show a beginning for analyzing the therapeutic prospects of miRNAs or anti-miRNAs. Generally, antitumor activity of miRNAs has been observed.