Engineered T Cells: CAR T Cell Therapy and Beyond

This article reviews the current data and future directions of engineered T cell therapies in non-Hodgkin lymphomas.Currently, four chimeric antigen receptor (CAR) T cell products are approved: axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel. These products differ in construct, indication, manufacturing, clinical trial design, and toxicity profile, but all are autologous products targeting CD19. Encouraging early data is also emerging with the use of these products in additional subtypes of B cell lymphoma. Alternative engineered T cell products are also in development, including dual CD19/22 targeting CAR T cells, CD30-directed CAR T cells, allogeneic CAR T cells, and engineered natural killer (NK) cells. Preclinical data using novel CAR constructs such as cytokine-secreting CARs targeted gene delivery into the T cell receptor α constant (TRAC) locus, combination strategies, and third-generation CARs holds promise for additional novel approaches. CAR T cells have transformed the therapeutic landscape for patients with relapsed/refractory B cell lymphomas. Early data with novel engineered cellular products is encouraging and holds promise for future clinical use.