Definition

A preparation of autologous T lymphocytes that are transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) cluster of differentiation 19 (CD19) and a programmed cell death protein 1 (PD1)/CD28 chimera, with potential immunomodulating and antineoplastic activities. Upon reintroduction into the patient, the autologous CD19/PD-1 bispecific CAR-T cells target and bind to CD19 and the PD-1 ligands, programmed cell death ligand 1 (PD-L1) and 2 (PD-L2), expressed on tumor cells. The binding to CD19 leads to a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells and cell lysis of these cells. The binding of the PD1/CD28 chimera to PD-L1 prevents the normal PD1/PD-L1-mediated T-cell suppression and, instead, promotes signaling through the CD28 domain, which results in the stimulation of T lymphocytes. This enhances T-lymphocyte proliferation and anti-tumor activity. CD19 antigen is a B-cell-specific cell surface antigen overexpressed in B-cell lineage malignancies. PD-1 protein, found on activated T-cells, negatively regulates T-cell activity. It plays a key role in immune evasion and prevents tumor cell lysis. The construct of the PD1/CD28 chimera converts PD-L1 into a co-stimulation ligand of primary human CD8+ cytotoxic T lymphocytes (CTLs). CD28 is a costimulatory molecule expressed by T cells that enhances T-lymphocyte proliferation and activity.