Caribou Biosciences, Inc. presents a poster of preclinical data demonstrating the promise of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy, as a therapeutic candidate for adult patients with relapsed or refractory acute myeloid leukemia (r/r AML). The presentation takes place at the 2023 American Association for Cancer Research (AACR) Annual Meeting from 1:30 pm to 5:00 pm EDT at the Orange County Convention Center, Orlando, Florida. Caribou's patented next-generation CRISPR Cas12a chRDNA genome-editing technology platform, which maintains high genomic integrity and significantly improves the specificity of genome edits, was used to engineer the 5 genome edits implemented in the manufacture of CB-012. CB-012 is the first allogeneic CAR-T cell therapy, to Caribou's knowledge, with both checkpoint disruption, through a PD-1 knockout (KO), and immune cloaking, through a B2M KO and B2M–HLA-E fusion transgene insertion.

These armoring strategies were designed to promote the durability of antitumor activity. Preclinical data presented at the AACR meeting show: CB-012 targets, becomes activated, proliferates, and demonstrates antitumor activity against a broad panel of AML cancer cell lines; Immune cloaking protects CB-012 from NK cell-mediated cytotoxicity; Mice harbouring AML xenograft models treated with CB-012 having a PD-1 KO showed extended survival relative to mice injected with control CAR-T cells that express PD-1 and that only contain 4 out of the 5 edits and CB-012 demonstrated significant antitumor efficacy and prolonged survival in AML xenograft models. About Caribou's Novel Next-Generation CRISPR Platform: CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells.

There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems have exhibited editing at unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced “chardonnays”) that direct substantially more precise genome editing compared to all-RNA guides.

Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.