Definition

A preparation of allogeneic T lymphocytes, depleted of CD45RA-positive cells, that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 (cluster of differentiation 19) fused to the co-stimulatory domain of 4-1BB (CD137) and the CD3-zeta (CD3z) T-cell signaling domain (4-1BBz), with potential immunostimulating and antineoplastic activities. CD45RA depletion results in a cellular product that contains a high amount of memory T cells (Tm). Upon administration, the allogeneic CD19-CAR CD45RA-negative T cells specifically recognize and bind to CD19-expressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen overexpressed in B-cell lineage malignancies. CD45RA is expressed on naive T cells (Tn), whereas Tm cells are CD45RA-negative. The depletion of the CD45RA-positive cells reduces the risk of graft-versus-host disease (GvHD) upon infusion. Tn cells have the potential to induce more severe graft-versus-host disease (GvHD) than Tm cells.