Caribou Biosciences, amidst setbacks from patient relapses, strategically pivoted towards a partially matched allogeneic product, setting it apart from conventional off-the-shelf options. While Caribou's primary focus remains on cancer therapeutics, the approval to explore CB-010 in autoimmune diseases marks a significant expansion of its scope.

CB-010, an allogeneic anti-CD19 CAR-T cell therapy, is derived from healthy donor T cells using cutting-edge CRISPR hybrid RNA-DNA (chRDNA) technology. This innovative approach involves three pivotal genome edits: knocking out TRAC to eliminate TCR expression, thereby reducing the risk of GvHD; inserting a CD19-specific CAR (scFv FMC63) into the TRAC locus; and targeting PD-1 knockout to prevent premature CAR-T cell exhaustion, potentially enhancing its antitumor activity.

With its allogeneic CAR-T cell therapy boasting partial HLA matching, CB-010 holds immense potential to match, or even surpass, the efficacy and safety profiles of approved autologous CAR-T cell therapies. The results presented at ASCO 2024 were as follows:

Efficacy outcomes:

After a single CB-010 infusion, patients achieved an overall response, achieved a CR, and achieved a CR at ≥6 months. Retrospective analyses of all patients enrolled in the ANTLER trial revealed that those who received CB-010 derived from a partial HLA-matched donor (i.e. ≥4 matching HLA alleles) showed improved progression-free survival (PFS) compared to patients who received CB-010 with ≤3 HLA matches.

Safety result: 

• CB-010 has a generally well-tolerated safety profile

• No Grade ≥3 cytokine release syndrome, no graft-versus-host disease observed

• Treatment-emergent adverse events (TEAE1) in ≥20% of all patients

KOL insights

“CB-010 demonstrated differentiated, long-term antitumor activity in preclinical studies. A single dose of CB-010 resulted in profound tumor regression of metastatic CD19 + tumor xenografts and led to a significantly longer antitumor response and survival vs. conventional CD19-specific allogeneic CAR-T cells (expressing PD-1)” – MD, director of lymphoma and CLL in the division of hematology and hematologic malignancies

“CB-010 with partial HLA matching shows safety, efficacy, and durability can potentially rival autologous CAR-T cell therapies.”– Professor of medicine and section chief of hematologic malignancies.

Conclusion- 

CB-010, Caribou Biosciences' 'off the shelf' therapy, holds great promise in the treatment landscape. Derived from healthy donor T cells and edited using Caribou's innovative Cas9 chRDNA technology, CB-010 presents a novel approach to addressing aggressive relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). By inserting a CD19-specific CAR into the TRAC gene and deleting the PD-1 gene, CB-010 enhances the immune response against cancer cells while mitigating their protective mechanisms.

As of April 1st, 2024, the clinical data underscores CB-010's potential as a viable therapeutic option for second-line large B cell lymphoma (LBCL) patients. With 46 patients treated across three dose levels and no observed Grade 3 adverse events or graft-versus-host disease, CB-010 demonstrates encouraging safety profiles. Moreover, the completion of the dose escalation phase and ongoing enrollment in the dose expansion phase signify significant progress. The upcoming presentation of initial dose expansion data and translational insights promises further elucidation of CB-010's efficacy and translational potential, heralding a new era in lymphoma treatment.