Autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T Cells - CISMeF
Autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T CellsNCIt concept
Preferred Label : Autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T Cells;
NCIt synonyms : CD19-CD8CD28zCAR-specific-mbIL15-HER1t T-lymphocytes; Autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-EGFRt T Cells;
NCIt definition : A preparation of autologous, genetically modified T-lymphocytes, that have been electroporated
ex vivo with sleeping beauty (SB)-derived DNA plasmids, expressing a second-generation
chimeric antigen receptor (CAR) composed of a mouse single-chain variable fragment
(scFv) specific for the tumor-associated antigen (TAA) cluster of differentiation
19 (CD19) that is linked to the co-stimulatory molecules T-cell surface glycoproteins
CD8 and CD28 and the zeta chain of the T-cell receptor (TCR)/CD3 complex (CD3-zeta)
and co-expressed with a chimeric membrane-bound fusion protein comprised of interleukin-15
(IL-15) fused to IL-15 receptor (mbIL15) and a safety/kill switch composed of a truncated
form of the human epidermal growth factor receptor (ErbB1t; EGFR) (HER1t), with potential
immunostimulating and antineoplastic activities. Upon reintroduction of the autologous
CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T cells into the patient, the T-cells target
and bind to CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing
tumor cells. CD19 is a B-cell specific cell surface antigen expressed in all B-cell
lineage malignancies. HER1t can promote selective elimination of the CAR-T cells through
cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent
cytotoxicity (CDC). IL-15 is a pro-survival cytokine that is required for the maintenance
of long-lived CD8 memory T-cells and use of mbIL15 preserves T stem-cell memory (TSCM)
through sustained IL-15 signaling, improves T-cell persistence and potentiates the
immune response against tumor cells. The SB system permits electroporation of the
CAR, the IL-15 fusion variant and safety switch transgenes into T-cells without the
need for viral vectors and accelerates the manufacturing process.;