Белакабнаген aранлейцел

Prop. INN (наименование, предложенное ВОЗ)

allogeneic natural killer (NK) cells obtained from peripheral blood mononuclear cells (PBMC) by leukapheresis, transduced with a non-replicating gamma (γ)-retroviral vector encoding a chimeric antigen receptor (CAR) targeting CD19 together with a membrane bound form of human interleukin-15 (mbIL15). The expressed transgene comprises a CD8 alpha (CD8α) leader sequence, a humanized anti-CD19 single-chain variable fragment derived from murine FMC63, a CD8α transmembrane domain, an OX40 costimulatory domain, and a CD3ζ signalling domain, separated by a self-cleaving T2A peptide from IL-15 fused to a CD8α transmembrane domain, which creates a membrane bound form of IL-15 (mbIL-15) under control of a promoter derived from the U3 region of the murine stem cell virus (MSCV) 5' long terminal repeat (LTR).
, The construct is flanked by 5' and 3' long terminal repeats (LTRs) and also contains a murine embryonic stem cell virus packaging signal.
, 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-12 (IL-12), interleukin-18 (IL-18) and 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 human AB serum and 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 CD19-beads

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