Investigating gene-edited CAR T cells as an effective therapy in cancer

Large B cell lymphoma (LBCL) is the most common type of non-Hodgkin lymphoma and causes a significant health burden. Cell-based therapies, including chimeric antigen receptor (CAR) T cells, have had great success treating B cell cancers, with about half of patients with lymphoma experience long-term clinical benefit. However, treatment of LBCL in individuals displaying significant extranodal disease (cancer presenting in peripheral tissues rather than/or in addition to lymph nodes) has been unfavourable and existing therapy must be improved. Thus, we have used a screening technique to identify genetic modifications that may promote CAR T cell functions in these difficult-to-treat sites. Candidate genes will be increased or blocked to produce more effective immunotherapy. CAR T cells harboring these beneficial gene modifications will be produced and their functional capacity assessed using culture-based assays. The modified CAR T cells will then be tested in mouse models of lymphoma to determine whether they have an enhanced ability to treat disease. The current study uses an innovative and unbiased method for discovery of targeted gene modifications that may be used in CAR T cell therapy to better treat extranodal B cell lymphoma.