Abstract

Exploiting the Patient-specific Tumor Mutanome for Individualized Vaccines for Cancer (IVACs)

John Castle, Co Director, The Institute for Translational Oncology and Immunology

Cancer arises from the accumulation of genomic mutations and the majority of metastatic cancers remain incurable. Clinical benefit may be substantial but temporary, supporting the general understanding that escape mechanisms occur when addressing single targets. Thus, there is a need for innovative concepts such as therapeutic vaccines targeting multiple tumor mutations. However, as more than 95% of mutations in a specific tumor (the mutanome) are unique to that patient, mutation-targeting therapeutic approach would be restricted to targeting those few mutations shared among multiple individuals. We have demonstrated the first preclinical proof-of-concept of a mutation-based individualized cancer vaccine that exploits the individuality of each tumor. The process involves NGS tumor exome and transcriptome sequencing to identify expressed non-synonymous somatic point mutations. Mutations are prioritized based on gene expression and predicted immunogenicity of mutation-containing peptides. The resultant patient-specific vaccine blueprint is synthesized “on-demand” under GMP conditions and encodes multiple mutation-containing peptides. We have shown the immunogenicity and tumor control of validated mutations in mouse models and tested the process in pre-clinical animal models and have now entered clinical trials.