Immunoinformatics Analysis of Citrullinated Antigen as Potential Multi-peptide Lung Cancer Vaccine Candidates for Indonesian Population.

Abstract

Non-small-cell lung cancer (NSCLC) is the most common lung cancer which has the highest mortality rate in Indonesia. One of the trends in treating cancer is by utilizing peptide vaccines, an immunotherapeutic approach that aims to stimulate the cell-mediated adaptive immune system to recognize cancer-associated peptides. Currently, no peptide vaccines are available in the market for NSCLC treatment. Therefore, this project aims to develop a multi-epitope peptide-based vaccine for NSCLC utilizing citrullinated peptides. Citrullination is a post-translational modification that occurs in cancer cells during autophagy that functions to induce immune responses towards modified self-epitopes such as tumor cells, through activation of PAD enzymes within the APC and target cells. It was found that introducing a common citrullinated neo-antigen peptide such as vimentin and enolase to the immune system could stimulate a higher specific CD4+ T cell response against NSCLC. Moreover, carcinoembryonic antigen (CEA), an antigen that is highly expressed in cancer cells, is also added to increase the vaccine's specificity and to mobilize both CD4+ and CD8+ T cells. These antigens bind strongly to the MHC Class II alleles such as HLA-DRB1*07:01 and HLA-DRB*11:01, which are predominant alleles in Indonesian populations. Through in silico approach, the peptides generated from CEA, citrullinated vimentin and enolase, were analyzed for their MHC binding strength, immunogenicity, ability to induce IFNγ response, and population coverage. It is expected that the immunodominant antigens presentation is able to induce a potent immune response in NSCLC patients in Indonesia, resulting in tumor eradication.