Dual CD19-CD70 CAR T Cells in Follicular Lymphoma
Araujo-Ayala F, Ros M, Alexandru R, et al. CD70 Overexpression at Diagnosis Predicts Relapse and Supports Dual CD19-CD70 CAR-T Therapy in Follicular Lymphoma. Blood. 2026; (doi: 10.1182/blood.2025032663).
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 and CD70 has the potential to improve outcomes in individuals with follicular lymphoma (FL) who have elevated relapse risk. By examining the immune microenvironment of patients at the time of FL diagnosis and following them for more than a decade, investigators recognized a shared trait in those prone to relapse. Specifically, CD70 overexpression in FL cells and in CD8+ and CD4+ T follicular helper cells at diagnosis was associated with inferior progression-free survival. Researchers subsequently theorized that dual CD19-CD70 CAR T cells might address these risk factors. In xenograft murine models of FL, the dual-CAR approach achieved complete tumor clearance in the spleen and bone marrow, outperforming single-target CAR-T cells. The dual CAR-T therapy demonstrated enhanced in vitro cytotoxicity against patient-derived spheroids of FL, diffuse large B-cell lymphoma, and mantle cell lymphoma.