Autologous CD19-CD8-CD28-CAR-mbIL15-HER1t T Cells - CISMeF
Autologous CD19-CD8-CD28-CAR-mbIL15-HER1t T CellsNCIt concept
Preferred Label : Autologous CD19-CD8-CD28-CAR-mbIL15-HER1t T Cells;
NCIt synonyms : RPM CD19 mbIL15 CAR-T Cells; RPM CD19-mbIL15-CAR T Cells; Rapid Personalized Manufacturing CD19-mbIL15-CAR T Cells;
NCIt definition : A preparation of autologous T-lymphocytes, that have been electroporated ex vivo with
sleeping beauty (SB)-derived DNA plasmids encoding a chimeric antigen receptor (CAR)
targeting 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 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-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 overexpressed 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 the 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.;