Over 18 months after first touting its allogeneic CAR-T approach, Crispr Therapeutics has started a clinical trial of its wholly owned candidate CTX110. The company joins Allogene, Cellectis, Celyad and Poseida in the off-the-shelf CAR-T therapy race, but Crispr believes its project to have an advantage over other assets. Crucially, according to the company, Crispr/Cas9 editing allows insertion of the CAR construct into a precise location. In the same step, this could disrupt endogenous T-cell receptors, preventing graft-versus-host disease, and also hit the cell’s major histocompatibility complex to prevent the CAR-T cells being destroyed by an immune response. CTX110, previously known as CTX101, is not the first Crispr/Cas9 engineered CAR-T contender to enter the clinic – that honour went to Tmunity’s autologous NY-ESO-directed T cells. There are a couple of other clinical-stage Crispr/Cas9-based projects, including Allergan and Editas’s AGN-151587, which began human trials last week in Leber congenital amaurosis 10, an inherited form of blindness. Editas has taken even longer to get its candidate into the clinic; having initially hoped to file an IND by the end of 2017. Editas also has an interest in CAR-T via a 2015 deal with Juno – now Celgene – but things have gone quiet here.
|Western trials of Crispr approaches|
|NY-ESO-1 redirected T cells||Tmunity||Autologous, ex vivo edited NY-ESO-targeting CAR-T therapy||Multiple myeloma, sarcoma, melanoma||NCT03399448|
|CTX001||Crispr Therapeutics/Vertex||Autologous, ex vivo edited haematopoietic stem cell therapy||Beta thalassaemia, sickle cell disease||NCT03655678, NCT03745287|
|AGN-151587/EDIT-101||Allergan/Editas||In vivo Crispr-based therapy||Leber congenital amaurosis 10||Brilliance, NCT03872479|
|CTX110||Crispr Therapeutics||Allogeneic, ex vivo edited CD19-targeting CAR-T therapy||B-cell malignancies||NCT04035434|
|Source: clinicaltrials.gov & company releases.|