107P Engineering CAR T cell therapy through novel co-stimulatory domains

CD19+ B cell-derived malignancies constitute a significant category of haematological cancers. CAR T cell therapy has improved outcomes but remains limited by relapse, off-target toxicity and poor persistence. These challenges are influenced by the co-stimulatory domain (CSD), which regulates activation, survival, and metabolism. Clinically utilised CAR T-cells incorporating CD28 or 4-1BB CSDs each offer distinct advantages and limitations. CD28 promotes rapid activation but results in limited persistence, whereas 4-1BB supports long-term persistence but slower effector function.