Identifying Patient-Specific Neoepitopes For Cell-Based And Vaccine Immunotherapy Targets In Breast Cancer Patients By Hla Typing And Predicting Mhc Presentation From Whole Genome And Rna Sequencing Data.

11606 Background: Anti-HER2 therapies have demonstrated success in improving the outcomes of patients (pts) with HER2-positive breast cancer; however, a high proportion of pts either do not respond to treatment or develop resistance to these agents. We developed an informatics platform that establishes HLA typing and predicts MHC presentation from whole genome sequencing (WGS) and RNA sequencing (RNAseq) data to identify neoepitopes among pts with HER2-positive breast cancer. Our platform provides a foundation for the development of next-generation, pt-specific cancer cell-based and vaccine immunotherapies. Methods: WGS and RNAseq data from The Cancer Genome Atlas (TCGA) were available for 19 HER2-positive breast cancer pts. Neoepitopes were identified by creating all permutations of 9-mer amino acid strings derived from identified single nucleotide variants and were filtered against all possible 9-mer peptide sequences created from every known human gene. In silico HLA typing was determined from WGS and RNAseq data using the HLA forest algorithm. NetMHC 3.4 was used to obtain the predicted binding affinities of neoepitopes to HLA alleles. Results: The numbers of predicted neoepitopes identified by WGS, neoepitopes expressed per RNAseq, and neoepitopes having binding affinity to any of the pts’ MHC class 1 HLA alleles were 10434, 5332, and 560, respectively, equivalent to an average of 9.8 high-quality neoepitopes per sample. The majority of neoepitopes were unique to each pt, with only 1 that was shared between 2 pts. Across all HER2-positive breast cancers, ~6% of neoepitopes occurred in cancer driver genes.Conclusions: We discovered that the majority of neoepitopes among pts with HER2-positive breast cancer were unique to each pt. For pts who do not respond to HER2-targeted agents, high-throughput identification of neoepitopes could serve as the basis for the development of pt-specific, cell-based and vaccine immunotherapies. Regardless of biomarker status or tissue of origin, all cancer pts may benefit from neoepitope-based immunotherapies.