CD19/ CD22 Bispecific CAR-T Cell Therapy for Relapsed/ Refractory Large B-cell Lymphoma

Overview

CAR-T cell therapy targeting CD19 has been shown to be effective in heavily-pretreated B-cell ALL or NHL, but relapses post-CAR-T are common, and CD19 antigen loss is one of the reasons. Thus, the investigators supposed that CD19/CD22 bispecific CAR-T cell therapy would be more effective and less relapses would occur in B- NHL. In this prospective phase 2 clinical trial, the investigators aim to explore the efficacy and safety of CD19/CD22 bispecific CAR-T cell therapy in relapsed/refractory Large B cell lymphoma.

Large B cell lymphoma (LBCL) is the most common aggressive subtype of non-Hodgkin lymphoma (NHL) in adults. While approximately 60% of patients can be cured with first-line therapy, a subset of patients experiences relapse or refractory disease (R/R). The prognosis for R/R LBCL patients is poor, with limited efficacy from traditional treatments such as autologous stem cell transplantation (ASCT) and novel targeted agents. Chimeric antigen receptor-T (CAR-T) cell therapy involves genetically engineering T cells to express chimeric antigen receptors (CARs) that target tumor-specific antigens, enabling precise elimination of tumor cells. CD19 is the most commonly targeted antigen in B-cell malignancies, however, antigen escape following CD19 CAR-T therapy can lead to disease relapse in some patients. Studies indicate that CD22 is widely expressed in B-cell malignancies and exhibits incomplete overlap with CD19 expression, suggesting that dual-target CAR-T therapy may more comprehensively eradicate tumor cells. Therefore, dual-target CAR-T therapy, particularly strategies targeting both CD19 and CD22, has emerged as a promising approach to overcome antigen escape and enhance therapeutic outcomes. In this prospective study, the investigators aimed to evaluate the efficacy and safety of CD19/CD22 bispecific CAR-T cell (CAR2219) therapy in patients with R/R LBCL.