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The paucity of mutations in pediatric and adult brain tumors has limited the ability to design therapeutic personal cancer vaccines. However, we have discovered that, in contrast to mutations in DNA, RNA is a rich source of frameshift neoantigens produced by mis-splicing of exons or indels from transcription through micro satellites. We have found that in GBM there are an average of 4000 such FS neoantigens per patient and in DIPG an average of at least 500 FS neoantigens/patient. Approximately 20% of these neoantigens are frequently recurrent across different patients. This has allowed us to design pre-synthesized vaccines for each tumor type. The vaccines consist of 20 -30 FS epitopes that are predicted to be present in at least 20% of all patient’s tumor. Each patient would have a 90% chance of having at least 50% of the peptides in their tumor. This type of “FAST” vaccine is much less expensive than a personal vaccine, any patient could be treated and there would be no delay in producing the vaccine. We have directly compared the efficacy of a FAST and personal vaccines in a mouse model of breast cancer. We find that both approaches have comparable protection though there are some interesting differences. We suggest that FAST vaccines may be a useful approach to developing therapeutic vaccines for brain cancers. We also demonstrate that an array of the 400K possible FS neoantigen peptides can be used to assay which neoantigens the patient has developed antibodies to. This array was useful in discovering the FAST vaccine components and could also be used to determine the pre-existing overlap of a FAST vaccine with the patient’s immune response.

ATIM-02. A NEW SOURCE OF NEOANTIGENS FOR PEDIATRIC AND ADULT BRAIN CANCER VACCINES