Фирикабтаген аутолейцел

Rec. INN (наименование, зарегистрированное ВОЗ)

autologous T lymphocytes obtained from peripheral blood by leukapheresis, transduced with a self-inactivating, non-replicating lentiviral vector encoding a chimeric antigen receptor (CAR) targeting human CD22. The expressed transgene comprises the granulocyte-macrophage colony-stimulating factor receptor subunit alpha (GMCSFR-alpha) signal sequence, an anti-CD22 single chain variable fragment (scFv), a CD8α hinge and transmembrane domain, a 4-1BB costimulatory domain and CD3ζ primary stimulatory 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 truncated gag, a Rev response element (RRE), a central polypurine tract (cPPT) sequence 5' to the transgene, and a partial nef/polypurine tract (PPT) sequence 3' to the transgene. The vector is pseudotyped with vesicular stomatitis virus (VSV) glycoprotein G.
The leukapheresis material is enriched for CD4/CD8 T lymphocytes by positive immunoselection, activated by CD3 and CD28 agonists and transduced with the lentiviral vector. The cells are then expanded in media containing human AB serum, interleukin 7 (IL-7) and 15 (IL-15). The T lymphocytes (≥70 % CD3+) are positive for the transgene (≥10% CAR positive), demonstrate cytotoxicity against CD22 expressing cells, and secrete interferon gamma in response to CD22 expressing tumour cell lines

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