Unique loop-structured CD19/CD22 bispecific CAR-T-cell therapy for patients with relapsed/refractory diffuse large B-cell lymphoma: An observational study

Although CD19 and CD22 chimeric antigen receptor (CAR-T) cell therapies have demonstrated encouraging clinical responses in patients with B-cell lymphoma, over 50% of patients ultimately experience disease progression due to frequent antigen escape. The development of CD19/CD22 dual-target CAR-T cells holds promise for overcoming this limitation; however, their clinical application is currently challenging because of insufficient targeting of CD22. In this study, we engineered CD19/CD22 BS Loop CAR-T cells with an enhanced targeting efficacy for CD22 and assessed their safety and effectiveness in patients with relapsed/refractory diffuse large B-cell lymphoma. Among the five patients who received CD19/CD22 bispecific loop CAR-T- cell therapy (1.6×106/kg) from December 2023 to May 2024, four patients (80%) achieved complete remission (CR), and one patient (20%) maintained a stable disease (SD) status one month after infusion. The expansion of the CD19/CD22 BS Loop CAR-T cells was effective in vivo and detectable in the peripheral blood. All patients experienced only grade 0–I cytokine release syndrome without any observed neurotoxicity. With the follow-up extended to May 2025 (lasting for at least 1 year), 3 patients experienced disease progression and eventually died, while the remaining 2 patients remained in complete remission. In conclusion, CD19/CD22 BS Loop CAR-T-cell therapy exhibits potent antilymphoma activity while addressing the challenges associated with designing CAR-T cells that are equally potent against two antigens. This treatment may represent a safe and effective unique immunotherapeutic strategy for lymphoma.