US FDA approves first non-gene edited allogeneic CAR T-cell candidate for trials
The US Food and Drug Administration (FDA) has accepted Celyad’s investigational new drug application for the first non-gene edited allogeneic CAR T-cell candidate, CYAD-101. The trial will investigate CYAD-101 in patients with unresectable colorectal cancer in combination with standard chemotherapy.
Allogeneic CAR T-cell therapy utilises cells manufactured from a healthy donor. The method could offer an alternative to autologous therapy, which Belgium-headquartered Celyad said can prove challenging for patients when the quality of the apheresis – the process which removes the stem cells – is poor.
French biotech Cellectis is also investigating allogeneic CAR T-cell candidates for large patient populations. However, unlike Cellectis’ gene-edited approach, Celyad does not cut the genome to knock out, or knock in, a gene, we were told.
“The mechanisms used to modify T-cells are thus different between the two companies. We are using a peptide called TIM (TCR inhibiting molecule), which is encoded alongside our chimeric antigen receptor. The cells are manufactured by transduction with one single vector coding for both components. We are not using any nuclease to edit the genome,” a Celyad spokesperson told us.
According to Celyad, the non-gene editing technology may be safer for patients: “Much remains to be understood concerning such manipulation of the genome,” we were told.
In addition, since gene-edited therapies require multiple rounds of genetic engineering, the manufacturing process can be laborious and technically challenging, the spokesperson said: “This [non-edited] approach offers significant advantages such as the absence of genetic manipulation, which saves time cost.”
Celyad did not disclose which third-party manufacturer will make CYAD-101 for clinical, and if successful, commercial supply.