Этивелкабтаген эригедлейцел

Prop. INN (наименование, предложенное ВОЗ)

allogeneic T lymphocytes obtained from peripheral blood mononuclear cells by leukapheresis of healthy donors, transduced with a self-inactivating, non-replicating lentiviral vector encoding two chimeric antigen receptors (CAR) in tandem, targeting CD20 and CD22, separated by a P2A peptide. The cells are also genetically modified using transcription activator-like (TAL) effector nucleases, which are transiently delivered into the cells as mRNAs to disrupt the T cell receptor alpha constant (TRAC) and CD52 genes., Each of the expressed CAR transgenes comprises a CD8α signal peptide, a single chain variable fragment (scFv) derived from a human monoclonal antibody, a CD8α hinge and transmembrane domain, and 4-1BB (CD137) and CD3ζ (CD247) intracellular costimulatory domains. The two transgenes are separated by a P2A ribosomal skip motif and are 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 and a mutated Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE). The vector is pseudotyped with vesicular stomatitis virus (VSV) glycoprotein G., The leukapheresis material is activated by CD3 and CD28 agonists and cultured in media containing serum and interleukin 2 (IL-2) prior to being transduced with the vector and expanded. Residual TCRab+ lymphocytes are removed by magnetic depletion. The suspension consists primarily of T lymphocytes with ≥30% CAR+, ≥39% CD52- and ≤3.0% TCRαβ+ T lymphocytes. The cells are cytotoxic, proliferate and secrete pro-inflammatory cytokines in response to CD20 and/or CD22-expressing cells.

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