Неспекабтаген аутолейцел

Prop. INN (наименование, предложенное 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) targeting CD19. The expressed transgene comprises a CD8α signal peptide, a humanized anti- CD19 single chain variable fragment (scFv) derived from scFv clone 1218, 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 (EF1α) promoter. The construct is flanked by 5' and 3' long terminal repeats (LTRs), and also contains a ψ packaging signal, a part of the human immunodeficiency virus (HIV) 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), a qPCR ID tag, and part of the HIV 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 (≥94%) with greater than 25% of the T lymphocytes expressing the CAR transgene. Cells exhibit anti- tumoral activity in patients with CD19-expressing B cell malignancies

Поделиться этой страницей