CRISPR Gene Editing is critical to delivering off-the-Shelf Cell Therapy

CRISPR Gene Editing is critical to delivering off-the-Shelf Cell Therapy ...

During the manufacturing process, cell therapies should be made off-the-shelf products that employ multiplex gene editing. That's according to Rachel Haurwitz, CEO of Caribou Biosciences.

Haurwitz, whose colleague Justin Skoble, PhD, spoke at the American Biomanufacturing Summit about innovative gene and cell therapy methods, believes that using CRISPR gene editing might result in off-the-shelf cell therapies that will significantly compete with individual patients.

CB-010 has three genome modifications: a deletion of the TRAC gene to target CD19 positive tumor cells; a knockout of PD-1 to boost CAR-T cell antitumor activity and potentially reduce CB-010 exhaustion. [Caribou Biosciences] The future of the cell therapy field should be off-the-shelf, which means [therapies] may be easier to fabricate.

Caribou Biosciences has developed a gene-editing system that uses CRISPR hybrid RNA-DNA guidelines to improve on traditional CRISPR Cas9 gene editing. According to Haurwitz, the chRDNA system allows Caribou to perform several gene edits to, for example, remove PD-1 from the surface of T-cells used in CAR-T cell therapies.

According to the author, the purpose of the cell therapy treatment is to keep the brakes on the cells so that it maintains strong tumor activity and improves clinical benefits.

She explains that with our next-generation CRISPR technology, chRDNA, she was able to integrate more gene edits, such as the PD-1 knockout, with high efficiency and specificity while maintaining the genome integrity [of the cells].

Caribou is the first company to require an off-the-shelf, or allogeneic, cell therapy after a PD-1 outbreak into the clinic, according to Haurwitz. They're also the only company currently employing hybrid guidelines for CRISPR.

In early June, the company provided initial clinical data for their allogeneic cell therapy, CB-010, for non-Hodgkin lymphoma. According to Haurwitz, the six patients in the study all responded to an initial dose of 40 million CAR-T cells.

For a starting phase I study, there's quite a low dose, and this is why all patients responded, and 40% of those patients continue to respond six months later.

According to Haurwitz, gene editing may help improve cell therapies' capabilities.

CB-011 is a multi-million dollar off-the-shelf product for multiple myeloma, and it requires four genome edits, two knockouts, and two insertions, according to the author. This is how was pushing the envelope of genome editing and deploying it in the manufacture of off-the-shelf cell therapy.

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