Date

Wednesday 08 Jan 2025

Time

15:15 - 15:45

Location

EM119

Supervisor

Sander van Kasteren

Jury

Kim Bonger

Two important classes of T-cell-engaging immunotherapies, the bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR-)T-cells, have emerged as innovative approaches in cancer treatment by recruiting effector T-cells to eliminate tumor cells. BiTEs are bispecific antibody-derived molecules targeting antigens on both T-cells and target cells, while CAR-T-cells are genetically engineered T-cells expressing chimeric receptors with target recognition and T-cell activation domains. Recently, BiTEs and CAR-T-cells have shown promise in addressing autoimmune diseases by depleting autoreactive lymphocytes or suppressing inflammation. This review gives an overview of these studies and compares the applicability and effectiveness of BiTEs and CAR-T-cells in the context of autoimmunity. CD19- and BCMA-targeting BiTEs and CAR-T-cells effectively eliminate antibody-producing lymphocytes, including autoantibody-producing plasmablasts and plasma cells, thereby addressing the root cause of many autoimmune disorders. However, the complete depletion of the B-cell compartment, as seen with CD19-targeting therapies, is associated with toxicities and adverse events which has spurred the development of more selective approaches. Novel concepts like Bi-specific AutoAntigen-T cell Engagers (BiAATEs) and chimeric autoantibody receptor (CAAR)-T-cells specifically target the small autoreactive B-cell population, while regulatory CAR-T-cells (CAR-Tregs) suppress inflammation in target tissues. These therapies have demonstrated preclinical efficacy and reduced toxicity profiles. Despite these advances, challenges remain in targeting autoreactive T-cells and achieving broader applications for BiTEs, which lag behind CAR-T-cells in development. However, BiTEs offer advantages in production, costs, associated toxicities, and structural modularity, enabling rapid adaptation for autoimmune contexts. With continued advancements, it could tentatively be stated that BiTEs and CAR-T-cells are poised to become essential tools for treating autoimmune diseases, potentially surpassing their success in oncology.