Grant: Doctoral Research Award: Canada Graduate Scholarships

Immunotherapy, which enhances a patient's own immune system, is a continuously promising treatment option for cancer. The immunotherapy known as chimeric antigen receptor (CAR) T cell therapy has shown success in curing patients with B cell cancers who had previously not responded to standard therapies. It works by re-targeting patient's T cells towards the cancerous B cells through the CAR, which is an engineered receptor that induces favourable function within T cells when they encounter the molecule targeted by the CAR. However, despite its success, most patients with large B cell lymphomas still fail to see long-term clinical benefit from CAR T cell therapy. Further analysis of contributing factors to CAR T cell failure in these patients found that those with the presence of lymphoma outside of the lymph nodes, termed extranodal lymphoma, have worse outcomes. We aim to generate CAR T cells that are better able to traffic to and kill lymphoma cells that are in other organs besides the lymph nodes, with hope that this will improve the overall clinical benefit of CAR T cell therapy for lymphoma. To do this, we intend to skew CAR T cells to be more like tissue resident memory T cells, a subset of T cells that are known to exist and form potent frontline defenses within a variety of tissues and are associated with better outcomes in most cancers. Using mouse models of lymphoma, we will test these new CAR T cells for their efficacy and phenotype across different tissues. With the induction of a tissue residency cell state, we hope to generate CAR T cells that can treat patients no matter where their lymphoma is.