Insilico Identification of MHC displayed Tumor Associated Peptides in Ovarian Cancer for Multi-Epitope Vaccine Construct

Abstract

Abstract One of the most prevalent gynaecologic malignancies with the greatest fatality rate is ovarian cancer. By recognizing the potential of immune system, immunotherapies have brought about a revolution in the treatment of cancer. However, interactions of malignant, non-malignant, and immune cells in the peritoneal cavity form a unique TME which is less explored in terms of immunosuppression. Less tumour mutational burden and strong immunosuppression in peritoneal TME leads to poor outcome of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Therefore, alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. The development of peptide vaccines based on tumor-associated antigens (TTAs) displayed in ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. This insilico study was conducted to find out potential epitopes for a peptide vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. In this investigation, we have selected MUC16, IDO1, FOLR1, and DDX5 for epitope prediction. Potential epitopes for B-cells, Helper T-lymphocytes (HTL) and Cytotoxic T-lymphocytes (CTL) were predicted on the basis of antigenic, allergenic, and toxic properties to design a multiepitope construct. The insilico evaluation of physicochemical properties and higher order structural analyses of the final construct revealed a potential vaccine candidate. The designed vaccine construct may be employed as a therapeutic immunization candidate for ovarian malignancies either alone or in combination with ICI. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.