Homology Modeling Epitopes of Kirsten Rat Sarcoma (KRAS) G12D, G12V and G12R as Pancreatic Ductal Adenocarcinoma Vaccine Candidates

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the world's deadliest cancers. Multiple studies demonstrated that PDAC is frequently characterized by the presence of Kirsten Rat Sarcoma (KRAS) G12D, G12V, and G12R protein mutants. The mutants are potential immunotherapy targets due to their potential as cancer-specific neoantigens. KRAS G12D, G12V and G12R contain vaccine-immunogenic epitopes. KRAS G12D, G12V and G12R epitopes were presented at major histocompatibility complexes (MHC) class I. The rational design of peptide vaccines to enhance the efficacy of cancer immunotherapy is facilitated by developing a peptide structural data library and knowledge of the MHC and antigen presentation processes. Before predicting peptide activity against MHC, homology modeling must transform the peptide into a three-dimensional structure. In this study, I-TASSER was used to perform homology modeling with the assistance of other applications. In silico methods for predicting epitopes to produce rationally designed peptide vaccines can increase the efficacy of these vaccines. This study yielded four epitope models that are potential PDAC vaccination candidates, KSFEDIHHYR, GIPFIETSAK, VVVGARGVGK and VVVGADGVGK.