ARI2h-TM28

ARI2h-TM28 is an experimental second-generation chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), developed by the Hospital Clínic de Barcelona and IDIBAPS. It is an optimized version of ARI0002h (cesni-cel), a BCMA-4-1BBζ CAR-T. The modification involves replacing the original CD8α transmembrane domain (TMD) with a CD28-TMD. This structural change is intended to facilitate dimerization with endogenous CD28, forming CAR-CD28 heterodimers that increase the sensitivity of the CAR-T cells to low-density BCMA antigens. Preclinical data presented at ASH 2024 indicate that ARI2h-TM28 exhibits superior tumor control and survival in multiple myeloma models compared to ARI0002h, particularly in scenarios with reduced BCMA expression.