Сенакнаген энфалеуцел

Prop. INN (наименование, предложенное ВОЗ)

allogeneic natural killer (NK) cells derived from peripheral blood mononuclear cells (PBMC) obtained by leukapheresis from healthy donors, transduced with a replication deficient murine stem cell virus (MSCV) derived γ-retroviral vector encoding (i) an activating chimeric receptor (ACR) composed of a CD8α signal peptide, the extracellular domain of the natural killer group 2, member D (NKG2D) receptor (also known as killer cell lectin-like receptor K1 (KLRK1)), fused to a CD8α transmembrane domain, an OX40 costimulatory domain and a CD3ζ signalling domain, and (ii) interleukin-15 (IL-15) preceded by a CD8α signal peptide and fused to a CD8α hinge and transmembrane domain, which creates a membrane bound form of IL-15 (mbIL-15), separated by a self-cleaving T2A peptide. The vector is pseudotyped with RD-114 virus envelope glycoprotein.
, The CD56+ CD3- NK cells are isolated by leukapheresis and co- cultured with a modified and irradiated K562 cell line.
, Specifically, the NK cells are isolated through a series of steps, first to reduce platelets and red blood cells, followed by a CD3+ depletion step, and lastly a positive selection using CD56+ enrichment. The cells are cultured in serum replacement media containing interleukin-2 (IL-2) and co-cultured with a modified and irradiated K562 cell line. The cells are then transduced with the retroviral vector, and the transduced NK cells are further expanded in media containing IL-2.
, The final substance consists of ≥90% CD56+CD3-NK cells with ≥20% CD56+ cells expressing the transgene. Cells secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF- α) when co-cultured with anti-NKG2D-beads

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