Recognition of tumor neoantigens is a major factor in the activity of clinical immunotherapies (Schumacher 2015). Therapeutic vaccines targeting neoantigens (Hacohen 2013) are showing promising results in clinical trials (Carreno 2015).
There are a few published pipelines for neoantigen identification (Hundal 2016), with accompanying open source software.
We'd like to improve the accuracy of neoantigen identification by comparing the performance and identifying the most informative stages of each pipeline.
We'll be collecting blood, somatic tissue, and tumor-infiltrating lymphocytes (TILs) from patients with a few different types of solid tumors. Whole-exome sequencing (WES) will be performed on the blood and somatic tissue and RNA-Seq will be performed on the somatic tissue.
A consolidated list of predicted neoepitopes will be built from all challenge submissions and a subset of those peptides will be synthesized and screened against the TILs from the patients using a proprietary assay. The final scoring algorithm has not been determined but will likely be related to the Normalized Discounted Cumulative Gain (NDCG) or F1 score. The results of the assay will be provided to all challenge participants.
Note that the primary goal of this challenge is to learn what pipeline stages are most informative for neoepitope identification, however, so in addition to scoring the final neoepitope lists we'll also be looking to see at which stage correct neoepitopes were filtered out.
The TILs present in an untreated tumor are different from those present in a tumor treated with checkpoint blockade or a personalized neoantigen vaccine.
To distinguish an incorrect epitope prediction from an epitope against which no immune response was mounted, it would be helpful to know the previous pathogen exposure and microbiome of the patient, as well as the capacity of their immune system to generate an immune response. It would also be helpful to know the immune contexture of the tumor, as a more immunosuppressive tumor microenvironment (TME) makes the possibility of no immune response more likely.
The proprietary T cell epitope discovery assay permits the phenotyping of T cells, so: perhaps. It would be useful to know if the T cells are activated, anergic, or exhausted.
We may selectively validate intermediate outputs such as predicted somatic mutations, HLA type, and peptide/MHC binding strength.
TN Schumacher, RD Schreiber. Neoantigens in cancer immunotherapy.. Science 348, 69-74 (2015).
N Hacohen, EF Fritsch, TA Carter, ES Lander, CJ Wu. Getting personal with neoantigen-based therapeutic cancer vaccines.. Cancer Immunol Res 1, 11-5 (2013).
BM Carreno, V Magrini, M Becker-Hapak, S Kaabinejadian, J Hundal, AA Petti, A Ly, WR Lie, WH Hildebrand, ER Mardis, GP Linette. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.. Science 348, 803-8 (2015).
J Hundal, BM Carreno, AA Petti, GP Linette, OL Griffith, ER Mardis, M Griffith. pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens.. Genome Med 8, 11 (2016).