Цесникабтаген аутолейцел

Prop. INN (наименование, предложенное ВОЗ)

autologous T lymphocytes obtained from peripheral blood mononuclear cells (PBMC) by leukapheresis, transduced with a self-inactivating, non-replicating lentiviral vector encoding a chimeric antigen receptor (CAR) targeting the B-cell maturation antigen (BCMA). The expressed transgene comprises an IgGκ chain V-III leader sequence, a humanized anti-BCMA single chain variable fragment (scFv, clone J22.9), a CD8α hinge and transmembrane domain, and a 4-1BB co-stimulatory domain and CD3ζ signalling domain, 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 ψ packaging signal, a Rev response element (RRE), a central polypurine tract (cPPT) sequence and a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The vector is pseudotyped with the vesicular stomatitis virus (VSV) G envelope protein.
The leukapheresis material is enriched for CD4+ and CD8+ T lymphocytes by positive immunoselection prior to activation with CD3 and CD28 agonists in growth media containing interleukin 7 (IL-7) and interleukin 5 (IL-5). The cells are then transduced with the lentiviral vector and expanded in growth media containing interleukin 7 (IL-7) and interleukin 5 (IL-5). The cell suspension consists of T lymphocytes (>70%), with greater than 20% of the T lymphocytes expressing the CAR-BCMA transgene. The transduced T lymphocytes demonstrate cytotoxicity against BCMA-expressing cells

Поделиться этой страницей