Leveraging TCR reactivity using viruses and vaccines to improve CAR T therapy

T cells patrol the body using their T cell receptors (TCR) to look for cells which display evidence of intracellular pathogens or cancers. In order to focus their attention on specific cancer antigens, T cells can be engineered to express an artificial recognition receptor (termed a Chimeric Antigen Receptor or CAR). CAR technology has been shown to be extremely powerful clinically in leukaemia and lymphoma patients who have not responded to other lines of therapy, leading to recent FDA and Health Canada approvals.

However, only one third of lymphoma patients treated with CD19 specific CAR T cells exhibit long lasting curative responses, thus leaving significant room for improvement. CAR T failure can usually be attributed to either loss of the tumour antigen (ie CD19) or to dysfunction of the T cells, and we are developing a strategy to address the latter. Once T cells express a CAR, they can still receive signals through their TCR, and we have shown in preliminary experiments that this type of stimulation can help CAR T cells to proliferate and kill tumour cells. Our research will use oncolytic cancer killing viruses, and other vaccines, to help mobilize CAR T cells which recognize viral antigens using their TCR.