Анитокабтаген аутолейцел

Rec. INN (наименование, зарегистрированное ВОЗ)

autologous T lymphocytes obtained from peripheral blood mononuclear cells by leukapheresis, transduced with a self-inactivating, non-replicating lentiviral vector encoding a chimeric antigen receptor (CAR) comprising a three-helix bundle D domain polypeptide (DDpp) targeting human B-cell maturation antigen (BCMA). The expressed transgene comprises a chymotrypsinogen B leader sequence, the anti-BCMA binding domain, a CD8α hinge and transmembrane domain, and a 4-1BB (CD137) and CD3ζ signalling domain, under control of the elongation factor 1 alpha (EF1α) promoter. The construct is flanked by 5' and 3' long terminal repeats (LTRs) and also contains a ψ packaging signal, a central polypurine tract (cPPT) sequence and a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The vector is pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein. The leukapheresis material is enriched for CD4+ and CD8+ T lymphocytes by positive immunoselection. The cells are then activated by CD3 and CD28 agonists and transduced with the lentiviral vector. The cells are further culture expanded in growth media containing interleukin 2 (IL-2) and human AB serum. The cell suspension consists of T lymphocytes (>83%), with greater than 10% of the T lymphocytes expressing the CAR-BCMA transgene. The transduced T lymphocytes demonstrate cytotoxicity against BCMA- expressing cells and secrete interferon gamma (IFN-γ) and IL-2

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