NCIt 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.;