2021–Therapeutic Neoantigens Encoded by Oncogene K-Ras — published on Science Immunology
K-Ras is one of the most highly mutated oncogenes in cancers. The neoantigens encoded by K-Ras can be presented by many different types of cancer cells. Here we utilized our multi-omics neoantigen validation pipeline to detect and quantify K-Ras neoantigens from a variety of cancer samples (Ref 1.). We found that the K-Ras as well as several other oncogenes can be presented on cancer cell surface, but at extremely low copy numbers. We adopted a variety of internal control system to measure their abundance down to <1 copy per cell level. To come up with an actionable strategy, the therapeutic team at JHU developed bispecific antibodies that can target the neoantigens we identified, and deliver dramatic therapeutic effects to mice. These findings are significant in the way that it opens a gate to developing pan-cancer immunotherapeutic agents that can treat a large number of patients sharing cancer hotspot mutations. Identifying such neoantigens is the first step in this campaign and is being accomplished by Complete Omics Inc.