Помлукабтаген аутолейцел

Rec. INN (наименование, зарегистрированное ВОЗ)

autologous T lymphocytes obtained from peripheral blood mononuclear cells by leukapheresis, transduced with a self-inactivating, non-replicating murine stem cell virus (MSCV) vector, encoding a chimeric antigen receptor (CAR) targeting human ganglioside GM2. The expressed CAR transgene comprises a leader sequence derived from a human immunoglobulin heavy chain, a human GM2-specific single-chain variable fragment (scFv), a human CD8 transmembrane domain, CD28, 4-1BB and CD3ζ intracellular signal motif. The vector genome also contains transgenes encoding human interleukin-7 (IL-7), human C-C motif chemokine 19 (CCL19) and herpes simplex virus- derived thymidine kinase transgene (HSV-tk), with each transgene separated by sequences encoding a foot and mouth disease 2A self-cleaving peptide. The construct is flanked by 5' and 3' long terminal repeats (LTRs) and expression is under the control of the 5' LTR promoter.
The leukapheresis material is enriched for CD3 T lymphocytes by positive immunoselection, and cultured in bags coated with anti-CD3 and recombinant human fibronectin, in media containing interleukin 2 (IL-2). The activated cells are transduced with the vector before further culture expansion in growth media containing IL-2. The cell suspension consists of T lymphocytes (>80%), with greater than 5% of the T lymphocytes expressing the anti-GM2 transgene. The T lymphocytes secrete interferon gamma (IFN-γ) and also transgene- derived IL-7 and CCL19 following co-culture with GM2-expressing cells.

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