Узатресген аутолейцел

Prop. INN (наименование, предложенное ВОЗ)

autologous CD3+ enriched T lymphocytes obtained from peripheral blood mononuclear cells (PBMCs) by apheresis. The cells are transduced with a self-inactivating, non-replicating lentiviral vector encoding an enhanced-affinity T cell receptor (TCR) targeting the HLA-A*02:01-restricted MAGE-A4 peptide (GVYDGREHTV) alongside the CD8 alpha (CD8ɑ) co-receptor.
The expressed transgene comprises the coding sequence for the CD8ɑ co-receptor, separated by a foot-and-mouth disease virus 2A self-cleaving peptide sequence from the coding sequence of the MAGE-A4 T-cell receptor alpha and beta chains that are separated from each other by a porcine teschovirus-1 2A self-cleaving peptide sequence, under control of the human elongation factor 1 alpha (EF-1α) promoter. The construct is flanked by 5' and 3' long terminal repeats (LTRs) and also contains a tRNA primer binding site, a ψ packaging signal, a truncated gag, a Rev response element (RRE) and a central polypurine tract (cPPT) sequence 5' to the transgene, and a polypurine tract (PPT) 3' to the transgene. The vector is pseudotyped with the vesicular stomatitis virus (VSV) G envelope glycoprotein.
The CD3+ T lymphocytes are purified and activated using anti-CD3/anti-CD28 monoclonal antibody coated magnetic beads. The cells are then cultured in media containing interleukin 2 (IL-2), human AB serum and a protein kinase B (AKT inhibitor). The cells are CD3+ (> 80%), express the high affinity MAGE-A4 specific TCR and CD8ɑ co-receptor (CD8ɑ +TCR+; >16%) and are cytotoxic to MAGE-A4 expressing tumor cells

Поделиться этой страницей