Anbal-Cel Demonstrates Clinical Activity in Relapsed LBCL

Anbalcabtagene autoleucel (anbal-cel), an investigational CD19-directed chimeric antigen receptor (CAR) T-cell therapy incorporating dual PD-1 and TIGIT knockdown, achieved a complete response (CR) rate of 67.1% in patients with relapsed or refractory large B-cell lymphoma (LBCL), according to findings from the phase 1/2 CRC01-01 trial (NCT04836507).¹

Findings published in Blood show that among 73 patients included in the phase 2 efficacy analysis, the overall response rate (ORR) was 75.3%, including a partial response in 8.2% of patients. Median progression-free survival (PFS) was 6.04 months (95% CI, 4.34-16.46), and median overall survival (OS) was not reached.

Anbal-cel is a CD19-directed CAR T-cell product incorporating short hairpin RNA-mediated knockdown of PD-1 and TIGIT through the OVIS (Overcome Immune Suppression) platform. By targeting these inhibitory receptors, the approach aims to limit mechanisms associated with T-cell exhaustion and support CAR T-cell activity. Unlike strategies that rely on administering separate checkpoint inhibitors, anbal-cel incorporates the knockdown approach into the CAR T-cell product itself. The therapy also contains a 4-1BB costimulatory domain.

About the Phase 1/2 Study

The multicenter study enrolled patients with relapsed or refractory LBCL who had received at least 2 prior lines of chemotherapy or experienced disease relapse after autologous hematopoietic stem cell transplantation.² Patients were enrolled between March 2021 and September 2023. In phase 1, 11 patients received 1 of 3 dose levels, ranging from 0.2 × 10⁶ to 2 × 10⁶ CAR-positive T cells per kg. No dose-limiting toxicities were observed, and 2 × 10⁶ cells per kg was selected as the recommended phase 2 dose.

In phase 2, 79 patients received anbal-cel, with 73 included in the efficacy analysis and all 79 included in the safety analysis. The population had substantial prior treatment exposure: 44.9% were refractory to first-line therapy, 64% were refractory to their most recent treatment, and 64.4% received bridging therapy before CAR T-cell infusion.

Additional Efficacy and Safety Data

At a median follow-up of 8.5 months, the 6-, 12-, and 18-month PFS rates were 50.9%, 41.1%, and 35.2%, respectively. Among patients achieving CR, the corresponding PFS rates were higher, at 64.5%, 55.6%, and 47.6%. The 12- and 18-month OS rates were 66.6% and 57.3%, respectively.

In the phase 2 safety population of 79 patients, 97.5% experienced grade 3 or higher adverse events. The most common were neutropenia (93.7%), thrombocytopenia (41.8%), and anemia (30.4%). Cytokine release syndrome (CRS) occurred in 57.0% of patients, including grade 3 events in 8.9%; no grade 4 or 5 CRS was reported. Neurological events occurred in 13.9% of patients, with grade 3 or higher events in 3.8%.

Serious infections occurred in 25.3% of patients, including 3 grade 5 infections. These findings underscore the importance of monitoring hematologic toxicity and infectious complications following treatment.

Anbal-Cel in the LBCL Treatment Landscape

Anbal-cel represents an approach to CAR T-cell engineering that targets multiple mechanisms of immune suppression within the cellular product. The exploratory findings from CRC01-01, including greater CAR T-cell expansion among responders and lower PD-1 and TIGIT expression among patients with sustained CR, provide clinical evidence supporting further investigation of this strategy. However, whether dual receptor knockdown translates into improved long-term outcomes compared with conventional CAR T-cell products remains to be established.

If validated in further studies, this engineering approach could offer another strategy for addressing CAR T-cell exhaustion, particularly in patients with heavily pretreated LBCL who may have limited treatment options.

REFERENCES

1. Kim WS, Kim SJ, Yoon DH, et al. Anbalcabtagene autoleucel (PD-1 and TIGIT knockdown CD19 CAR T-cell therapy) for relapsed or refractory LBCL: the CRC01-01 trial. Blood. 2026;148(17):2132-2145. doi:10.1182/blood.2025032636

2. Study of Efficacy and Safety of CRC01 in Adult Large B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia Patients. ClinicalTrials.gov. Updated July 1, 2026. Accessed November 10, 2026. https://clinicaltrials.gov/study/NCT04837650