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- B582a0ff4011c35a27d2cb5d5abe1d7e9 NCIT_P378 "NCI" @default.
- B582a0ff4011c35a27d2cb5d5abe1d7e9 type Axiom @default.
- B582a0ff4011c35a27d2cb5d5abe1d7e9 annotatedProperty IAO_0000115 @default.
- B582a0ff4011c35a27d2cb5d5abe1d7e9 annotatedSource NCIT_C180672 @default.
- B582a0ff4011c35a27d2cb5d5abe1d7e9 annotatedTarget "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." @default.