Ресекабтаген аутолейцел

Prop. INN (наименование, предложенное ВОЗ)

autologous T lymphocytes derived from peripheral blood mononuclear cells obtained by leukapheresis, transduced with a self-inactivating, non-replicating lentiviral vector encoding a chimeric antigen receptor (CAR) targeting CD19., The expressed transgene comprises a CD8α signal peptide, an anti-CD19 humanised single chain variable fragment (scFv) (clone IC78), a CD8α hinge and transmembrane region, and a 4- 1BB co-stimulatory domain and CD3ζ signaling domain, under control of the elongation factor-1 alpha (EF-1α) promoter. The construct is flanked by 5' and 3' long terminal repeats (LTRs) and also contains an HIV-1 ψ packaging signal, part of the HIV-1 gag and env genes, a Rev response element (RRE), a central polypurine tract/central termination sequence (cPPT/CTS), a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) and the nef gene. 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 supplemented with serum replacement and interleukin 2 (IL-2). The cell suspension consists of T lymphocytes (≥80%) with greater than 10% of the T lymphocytes expressing the CAR transgene, other cell types (expressing CD16, CD14 and CD19) are present at ≤20%, and memory T lymphocyte subsets are phenotypically determined., The cells exhibit cytotoxicity towards CD19 expressing B lymphocytes upon co-culture

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