Identifying Patient-Specific Neoepitopes For Cell-Based And Vaccine Immunotherapy Across Breast Cancer Classifications Reveals Rarely Shared Recurrent Neoepitopes

Abstract Introduction: Targeted therapies for breast cancers such as trastuzumab and everolimus have durable clinical benefits for patients that express the relevant biomarkers (HER2 and mTOR respectively). Triple negative breast cancer patients lack these biomarkers and are left with few options. Recent advances in immunotherapy agents against PD-1/CTLA4 for patients with melanoma have yielded amazing clinical benefits for a subset of patients and may have similar results in breast cancer patients, but again the vast majority of patients still undergo disease progression. We analyzed whole genome sequencing (WGS) and RNA sequencing data from The Cancer Genome Atlas (TCGA) to identify neoepitopes among breast cancer patients that could be used to develop next-generation, patient-specific cancer immunotherapies. Neoepitopes are tumor specific markers that arise from mutations acquired from cancer and may represent a path to targeted therapies even in triple negative breast cancers. Results: We analyzed 99 breast cancer patients from TCGA, containing a mixture of PR+/HER2+/ER+ and TNBC classifications. These breast cancer patient samples were selected by the availability of whole genome sequencing (WGS) data, RNA-sequencing data as well as clinical outcome data. We identified an average of 680 potential neoepitopes per patient based solely on WGS data. To further refine and select high quality neoepitopes we restricted these neoepitopes based on gene expression yielding an average of 304 expressed neoepitopes per patient. We predicted each patient's HLA typing using only omics data, which we then used to predict HLA-expressed neoepitope binding analysis resulting in an average of 11 high-quality tumor specific neoepitopes per patient. We identified few recurrent neoepitopes that were bound and expressed, indicating the need for a personalized medicine approach. Conclusions: Within the TCGA dataset, the majority of neoepitopes among patients with breast cancer were unique to each patient. Rarely within subsets of breast cancers such as HER2+, we identify neoepitopes that are shared between patients. For breast cancer patients who do not respond to targeted therapies, high-throughput identification of neoepitopes could serve as the basis for the development of next-generation, patient-specific immunotherapies. Citation Format: Nguyen A, Sanborn JZ, Vaske CJ, Rabizadeh S, Niazi K, Soon-Shiong P, Benz SC. Identifying patient-specific neoepitopes for cell-based and vaccine immunotherapy across breast cancer classifications reveals rarely shared recurrent neoepitopes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-26.