TY - JOUR
T1 - Experimental analysis of T cell epitopes for designing liver cancer vaccine predicted by system-level immunoinformatics approach
AU - Muhammad, Syed Aun
AU - Zafar, Sidra
AU - Rizvi, Samana Zahra
AU - Imran, Imran
AU - Munir, Fahad
AU - Jamshed, Muhammad Babar
AU - Ali, Amjad
AU - Wu, Xiaogang
AU - Shahid, Numan
AU - Zaeem, Muhammad
AU - Zhang, Qiyu
N1 - Publisher Copyright:
Copyright © 2020 the American Physiological Society.
PY - 2020/6
Y1 - 2020/6
N2 - 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. immunoassays immunoinformatics approach; liver cancer; peptide modeling; T cell epitopes.
AB - 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. immunoassays immunoinformatics approach; liver cancer; peptide modeling; T cell epitopes.
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U2 - 10.1152/AJPGI.00068.2020
DO - 10.1152/AJPGI.00068.2020
M3 - Article
C2 - 32363891
AN - SCOPUS:85086356190
SN - 0193-1857
VL - 318
SP - G1055-G1069
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 6
ER -