Clinical Trial Update: Caribou’s CB-010 Rivals Response Rates and Safety Profiles of Approved Autologous CAR-T Cell Therapies

Last week, Caribou Biosciences reported positive long-term follow-up data from the dose escalation portion of the ongoing ANTLER Phase 1 trial. The trial, which commenced in May 2021, is evaluating Caribou's lead allogeneic CAR-T cell therapeutic candidate CB-010 for the treatment of relapsed or refractory B cell non-hodgkin lymphoma (r/r B-NHL).

The new data set includes all 16 patients with aggressive r/r B-NHL who were treated with one of three dosing levels of CB010 (40x10⁶, 80x10⁶, and 120x10⁶ CAR-T cells). Each of these 16 patients had either received two or more prior lines of chemoimmunotherapy or were primary refractory patients (i.e. never achieved a complete remission from any therapy).

In its press release, Caribou Biosciences states that data for CB-010 rivals response rates and safety profiles of approved autologous CAR-T cell therapies, with an overall response rate of 94 % and a complete response rate of 69 % after a single dose of CB-010.

First PD-1 knockout CAR-T candidate to enter clinical trial

CB-010 is designed to be an 'off' the shelf' therapy, which is derived from healthy donor T cells that are edited using Caribou's proprietary Cas9 chRDNA technology.

Unlike conventional CRISPR-Cas gene editing, which involves the use of all-RNA guides, Caribou uses CRISPR hybrid RNA-DNA guides (chRDNAs), which are generated by carefully introducing DNA into the backbone of an RNA guide (Figure 1).

chRDNA technology was developed following discoveries by Caribou scientists that strategically introducing DNA into an RNA guide led to a detuning of the affinity when there's a mismatch between the guide RNA and a region of genomic DNA. You can read more about Cas9 chRDNA in our interview with Caribou's CSO Steve Kanner Ph.D. here.

To generate CB-010, a CD19-specific CAR is inserted into the TRAC gene (which encodes the T cell receptor alpha constant) of healthy donor T cells. The PD-1 gene is also deleted in these cells. This gene encodes the PD-1 protein that functions as a safety switch on T cells that cancer cells turn on to protect themselves from T cell-mediated immune responses. In 2020, CB-010 became the first allogeneic CAR-T cell therapy with a CRISPR-mediated PD-1 deletion to receive FDA clearance for clinical trial initiation.