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RNA Transcription and Splicing Errors as a Source of Cancer frameeshift Neoantigens for Vaccines ns for Vaccines

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


Fatemeh Babaie

Abstract | PDF

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