Призлонкабтаген аутолейцел

Rec. INN (наименование, зарегистрированное ВОЗ)

autologous T lymphocytes obtained from peripheral blood lymphocytes by leukapheresis, transduced with a self- inactivating, non-replicating lentiviral vector, encoding a bispecific chimeric antigen receptor targeting CD19 and CD20.
The expressed transgene comprises a CD8α leader sequence, anti-CD19 and anti-CD20 single chain fragment variable (scFv) (derived from FMC-63 and ofatumumab, respectively), an IgG4 hinge and a CD28 transmembrane region, a 4-1BB and a CD3ζ signalling domain, and is under control of the elongation factor 1 alpha (EF1α) short 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 mutated Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE).
The vector is pseudotyped with vesicular stomatitis virus (VSV) G envelope protein. 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 with serum replacement and interleukin 2 (IL-2). The T lymphocytes (≥95%) are positive for the transgene (≥10% CAR positive), and secrete interferon gamma in response to CD19 and CD20 expressing tumour cell lines

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