It has been recognized for nearly three decades that patients with tumours that are strongly infiltrated by T cells, in particular cytotoxic T cells, have better outcomes. We use computational approaches and targeted immunoassays in the lab to gain insights into the nature of the anti-cancer T cell response, and to determine how and why it varies among healthy individuals and among cancer patients. These studies inform our programs for pre-clinical and clinical development of genetically engineered T cell therapies, including chimeric antigen receptor (CAR-T) and recombinant T cell receptor (rTCR) therapies for cancer.
We are particularly focused on using rTCRs to target cancer hotspot mutations. These are mutations that are seen in certain cancers at high frequency, which is unusual because most cancer mutations are random. We are systematically assessing hotspot mutations for their immunogenicity using a combination of genomics, mass spectrometry, flow cytometry and cellular immunoassays. We are optimizing procedures of isolating, expanding, activating, and redelivering these mutation-reactive T cells as targeted immunotherapies