CAR T-cells Targeting the CD4 Protein Granted FDA Orphan Drug Designation

The indication concerns the treatment of peripheral T-cell lymphoma

iCell Gene Therapeutics announced on 11 August 2016 that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation for its chimeric antigen receptor engineered T-cells directed against the target protein CD4 (CD4CAR) for the treatment of peripheral T-cell lymphoma (PTCL).

The Orphan Drug Designation programme provides orphan status, and associated development incentives, to drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders.

A chimeric antigen receptor (CAR) engineered T-cell is a patient's T-cell that has been genetically modified to express a protein on its surface with the capability to bind to a target protein on another cell. Upon binding, the CAR protein will send a signal across the cell membrane to the interior of the T-cell to set in motion mechanisms to selectively kill the targeted cell.

Although there are clinical development programmes ongoing with CAR T-cells for CD19+ cell haematological malignancies, CD4+ PTCLs have not been targeted by a CAR therapy in a human trial. PTCLs account for 10–15% of all non-Hodgkin’s lymphomas (NHLs) and are more difficult to treat in comparison to B-cell NHLs. Furthermore, and with few exceptions, T-cell NHLs have poorer outcomes, lower response rates, shorter times to progression, and shorter median survival in comparison to B-cell NHLs. As a result, the standard of care for PTCLs is not well-established and the only potential curative regimen is bone marrow transplant (BMT). Not only is BMT poorly-tolerated, but is not an option for a significant subset of patients with resistant disease. This leaves many patients with no curative options.

Cancer researchers from some US academic sites partnered with the iCell Gene Therapeutics to lead this cutting-edge immunotherapy into first-in-human clinical trial for patients suffering this extremely difficult to treat T cell lymphoma.

CD4CAR is in development for CD4+ T-cell malignancies. The novel CD4-specific chimeric antigen receptor engineered T-cells are properly-matched allogeneic human T-cells engineered to express an anti-CD4scFV antibody domain. An initial phase I clinical study is being planned through collaboration between iCell Gene Therapeutics, the US National Institutes of Health, Indiana Clinical and Translational Sciences Institute, Stony Brook Hospital, the Blood and Marrow Transplantation Division and the Clinic Trial Research Unit at James Graham Brown Cancer Center at University of Louisville.