Золакабтаген аутолейцел

Prop. INN (наименование, предложенное ВОЗ)

autologous CD4+ and CD8+ T lymphocytes obtained by leukapheresis and transduced with a self-inactivating, non- replicating lentiviral vector encoding (i) a CD19 specific chimeric antigen receptor (CAR) and (ii) truncated human epidermal growth factor receptor (EGFRt) separated from the CAR by a T2A self- cleaving peptide, under control of a chimeric promoter composed of the elongation factor 1 alpha (EF-1α) promoter/R region of the human T cell leukaemia virus 1 (HTLV-1 R) and a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The CD19-specific CAR transgene consists of a single-chain variable fragment (scFv) derived from a CD19-specific monoclonal antibody (FMC63), an IgG4 hinge region, a CD28 transmembrane domain, and the intracellular CD137 (4-1BB) co-stimulatory and CD3ζ signalling domains. Both transgenes, the CD19-specific CAR and the EGFRt, are preceded by human granulocyte-macrophage colony-stimulating factor receptor alpha (GMCSFR-alpha) signal peptide sequence. The vector genome also contains a psi packaging signal, a splice donor, partial gag, Rev response element (RRE), a DNA FLAP, and a splice acceptor. The vector is flanked by 5' and 3' long terminal repeats (LTRs) and is pseudotyped by vesicular stomatitis virus (VSV) G glycoprotein.
, The leukapheresis material is sorted to co-select the CD4+ and CD8+ T lymphocytes by positive immunoselection prior to activation with CD3 and CD28 agonists in growth media containing interleukin 2 (IL-2), interleukin 7 (IL-7) and interleukin 15 (IL-15).
, The mixed CD4+/CD8+ cells are then transduced with the lentiviral vector and minimally expanded in growth media containing IL-2, IL- 7 and IL-15. The cell suspension consists of CD4+ and CD8+ lymphocytes that are ≥80% CD3+ and contain ≥10% CD3+CAR+ cells. The transduced T lymphocytes release interferon gamma (IFN-γ) by co-culture with target cells in vitro

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