On August 1, Universal CAR-T (UCAR-T) pioneer Cellectis announced that the U.S. FDA has approved the company’s IND application for UCART20x22 to initiate this product candidate for relapsed or refractory non-Hodgkin lymphoma (r /r NHL) in a phase I/IIa clinical trial. Cellectis plans to enroll patients in the NatHaLi-01 study in the second half of this year. The Dose Finding portion of the study will assess the role of UCART20x22 in a broad spectrum of mature B-cell NHL, a lymphoma that accounts for approximately 4% of all cancers.
UCART20x22 is Cellectis’ first dual-target general-purpose CAR-T product candidate to enter clinical development, targeting both CD20 and CD22 (both effective targets in B-cell malignancies), with the potential to enhance tumor cell lethality and increase antigenicity Breadth of targeting; it is also the company’s first fully in-house developed product candidate, demonstrating Cellectis’ transformation into an end-to-end cell and gene therapy company (from discovery, process development and GMP manufacturing to clinical development).
UCART20x22 is characterized by TALEN®-mediated disruption of the TRAC and CD52 genes. TRAC gene refers to the T cell receptor alpha constant region, and knocking out this gene means that the T cell receptor (TCR) on the surface of T cells is eliminated, thereby avoiding the occurrence of graft-versus-host disease (GVHD). Before the infusion of universal CAR-T cells, the use of CD52 antibody can remove T cells and NK cells in the host, and with the knockout of CD52 molecules on universal CAR-T cells, CD52 targets can be used in the patient’s conditioning regimen. To monoclonal antibody (alemtuzumab), enhance CAR-T engraftment, expansion and persistence.
Dr. André Choulika, CEO of Cellectis, said UCART20x22 would be a potential alternative to CD19-targeted therapy.