In silico Identification of MHC Displayed Tumor Associated Peptides in Ovarian Cancer for Multi-Epitope Vaccine Construct.

BACKGROUND:Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. INTRODUCTION:The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in-silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. METHODS:The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected as potential epitopes for B-cells, helper T-lymphocytes (HTLs), and cytotoxic T-lymphocytes (CTLs) predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct. RESULTS:Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were predicted from the TAAs. The designed multi-epitope construct was potentially immunogenic, non-toxic, and nonallergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate. CONCLUSION:The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.