Фенкабтаген аутолейцел

Rec. INN (наименование, зарегистрированное ВОЗ)

autologous CD4/CD8 enriched T lymphocytes obtained from peripheral blood by leukapheresis, transduced with a self- inactivating, non-replicating lentiviral vector encoding a chimeric antigen receptor targeting human receptor tyrosine-protein kinase erbB-2 (also known as epidermal growth factor receptor 2 (HER2)).
The expressed transgene comprises a human immunoglobulin G (IgG) leader sequence, an extracellular HER2-binding domain provided by a designed ankyrin repeat protein, a human c-Myc tag sequence, an anti-T cell receptor (TCR)/CD3ε binding domain provided by the humanized UCHT1 single-chain antibody fragment (scFv), and a CD4 co-receptor membrane anchoring and intracellular domain, under the control of the murine stem cell virus (MSCV) promoter.
The construct is flanked by 5' and 3' long terminal repeats (LTRs) and also contains a ψ packaging signal, a truncated gag, a Rev response element (RRE), a central polypurine tract (cPPT) sequence, a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) and a synthetic ID tag sequence. The vector is pseudotyped by vesicular stomatitis virus (VSV) glycoprotein G.
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 with serum replacement containing interleukin 2 (IL-2) and 7 (IL-7). The cell suspension consists of T lymphocytes (>96% CD3+) with greater than 10% (average 45%) of the T lymphocytes expressing the transgene

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