autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T cells

{
  "id": "MLC-T-ONC-011543",
  "term": "autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T cells",
  "field": "Oncology and biomedicine",
  "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.",
  "synonyms": [
    "CD19-CD8CD28zCAR-specific-mbIL15-HER1t T lymphocytes",
    "autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-EGFRt T cells"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/autologous-cd19-cd8-cd28-cd3zeta-car-mbil15-her1t-t-cells/"
}