RNA Transcription and Splicing Errors as a Source of Cancer Frameshift Neoantigens for Vaccines
Abstract
The success of checkpoint inhibitors in cancer therapy is largely attributed to activating the patient’s immune response to their tumor’s neoantigens arising from DNA mutations. This realization has motivated the interest in personal cancer vaccines based on sequencing the patient’s tumor DNA to discover neoantigens. Here we propose an additional, unrecognized source of tumor neoantigens. We show that errors in transcription of microsatellites (MS) and mis-splicing of exons create highly immunogenic frameshift (FS) neoantigens in tumors. The sequence of these FS neoantigens are predictable, allowing creation of a peptide array representing all possible neoantigen FS peptides. This array can be used to detect the antibody response in a patient to the FS peptides. A survey of 5 types of cancers reveals peptides that are personally reactive for each patient. This source of neoantigens and the method to discover them may be useful in developing cancer vaccines.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 02, 2019
- Source ID
- 10.1038/s41598-019-50738-4
Entities
People
- HoJoon Lee
- Jian Zhang
- Luhui Shen
- Milene Tavares Batista
- Stephen Albert Johnston
Organizations
- United States Department of Defense
- W. M. Keck Foundation