Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma

Area of Science:

• Immunotherapy
• Oncology
• Cellular Therapy

Background:

• Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has shown promise for hematological malignancies like relapsed/refractory non-Hodgkin lymphoma (r/rNHL).
• High rates of treatment failure and recurrence remain significant challenges in CAR T-cell therapy for r/rNHL.
• Novel CAR T-cell designs are needed to overcome resistance and improve durable responses.

Purpose of the Study:

• To design and evaluate a novel tandem CAR (TanCAR) T-cell therapy for r/rNHL.
• To assess the safety, tolerability, and preliminary efficacy of TanCAR7 T cells in a phase 1/2a clinical trial.
• To investigate the potential of dual antigen targeting (CD19 and CD20) for enhanced antitumor activity.

Main Methods:

• Development of tandem CARs (TanCARs), specifically TanCAR7 T cells, for dual targeting of CD19 and CD20.
• Enrollment of 33 patients with r/rNHL in an open-label, single-arm phase 1/2a trial (NCT03097770).
• Evaluation of safety (primary endpoint) and efficacy, including overall response rate (ORR), complete response rate (CR), progression-free survival (PFS), and overall survival (OS) (secondary endpoints).

Main Results:

• TanCAR7 T cells exhibited dual antigen targeting of CD19 and CD20 and formed stable immunological synapse (IS) structures.
• The overall response rate (ORR) was 79% (95% CI, 60-92%), with a complete response (CR) rate of 71%.
• Grade 1 or 2 cytokine release syndrome (CRS) occurred in 36% of patients, and grade 3 CRS in 14%. No grade 3 or higher CAR T-cell-related encephalopathy syndrome (CRES) was observed. One treatment-associated death occurred due to severe pulmonary infection.

Conclusions:

• TanCAR7 T cells demonstrate potent and durable antitumor activity in patients with r/rNHL.
• The dual-targeting strategy and enhanced IS formation may contribute to the observed robust efficacy.
• TanCAR7 T cells offer a promising safety profile with manageable CRS and no high-grade CRES, warranting further investigation in r/rNHL treatment.