Рондекабтаген аутолейцел

Prop. INN (наименование, предложенное ВОЗ)

autologous T lymphocytes obtained by leukapheresis enriched for the cell surface marker CD62L (also known as L-selectin) transduced with a self-inactivating non-replicating lentiviral vector encoding a tandem chimeric antigen receptor (CAR) targeting both CD20and CD19 [comprising a single chain variable fragment (scFvs) derived from the antibody clone Leu16 fused via flexible linkers to a scFvs derived from clone FMC63]. The transgene has a murine immunoglobulin kappa (mIgK) leader sequence and also comprises an IgG4 hinge, a CD28 transmembrane, and the intracellular 4-1BB co- stimulatory and CD3ζ signaling domains and is under control of the elongation factor 1 alpha (EF-1α) promoter and the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) modified to eliminate the X-protein open reading frame. The vector genome also contains a human immunodeficiency virus (HIV) packaging signal, a Rev response element (RRE), central polypurine tract and central termination sequence (cPPT/CTS) and is flanked by 5' and 3' long terminal repeats (LTRs). The vector is pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein.
, The leukapheresis material is enriched for CD62L expressing T lymphocytes by positive immunoselection and cultured in media containing interleukin 2 (IL-2) and interleukin 15 (IL-15). The lymphocytes are activated by CD3 and CD28 agonists and transduced with the lentiviral vector followed by culture in media containing IL-2 and IL-15. The T lymphocytes (≥80%) are predominantly composed of naïve and central memory rich T lymphocyte subsets as measured by expression of CD62L and CD45RA surface markers, and positive for the transgene (≥10% CAR positive) with few (<5%) CD19 expressing B lymphocytes. The cells exhibit cytotoxicity and secrete interferon gamma in response to CD19 and CD20 expressing tumour cell lines

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