CRISPR Gene Editing Critical to Delivering Off-the-Shelf Cell Therapy
The future of cell therapies should be in off-the-shelf products using multiplex gene editing during the manufacturing process. Gene editing can improve the specifications of cell therapies. The cell therapy field should be off-the-shelf, which means can be available to a larger patient community. Off-the-shelf therapies are also seen as simpler to manufacture.
Caribou Biosciences has developed a gene-editing system that uses CRISPR hybrid RNA-DNA (chRDNA) guides to improve on traditional CRISPR Cas9 gene editing. The chRDNA system allows to conduct of multiple gene edits to, for example, remove PD-1 from the surface of T-cells used in CAR-T cell therapies. With our next-generation CRISPR technology, called chRDNA, we’re able to integrate more gene edits, such as PD-1 knockout, with high efficiency and specificity, while maintaining genomic integrity. Caribou is the first company to take an off-the-shelf, or allogeneic, cell therapy with a PD-1 knockout into the clinic. They’re the only company currently using hybrid guides for CRISPR.
In early June, the company presented initial clinical data for their allogeneic cell therapy, CB-010, for non-Hodgkin lymphoma. The six patients in the study all responded to an initial single dose of 40 million CAR-T cells. That’s quite a low dose for a beginning Phase I study, so it’s remarkable all patients responded.
CB-010 interaction with B cell non-Hodgkin lymphoma cells:
Using Caribou’s chRDNA technology, CB-010 has three genome edits:
1. A deletion of the TRAC gene to remove T cell receptors.
2. Insertion of a CD19-specific CAR into TRAC locus to target CD19-positive tumor cells.
3. A knockout of PD-1 to boost the persistence of CAR-T cell antitumor activity.
CB-010 has three edits, two knockouts, and one insertion. Their next program, CB-011, an off-the-shelf product for multiple myeloma, requires four genome edits, two knockouts, and two insertions.
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