Dr. Holt’s lab is using deep sequencing and novel computational methods to identify the spectrum of somatic mutations in various cancers, with a particular focus on tumour evolution and the identification of antigens for cancer vaccines. While most tumour mutations are sporadic, some hot-spot mutations are seen in certain cancers at high frequency. The group is systematically assessing the most highly recurrent cancer mutations for their immunogenicity using a combination of mass spectrometry, flow cytometry and cellular immunoassays. They are optimizing procedures for isolating, expanding, activating and redelivering these mutation-reactive T cells as targeted immunotherapies.