Сувутресген аутолейцел

Rec. INN (наименование, зарегистрированное ВОЗ)

autologous T lymphocytes obtained from peripheral blood lymphocytes by leukapheresis, transduced with a self- inactivating, non-replicating lentiviral vector encoding an affinity- enhanced cancer testis antigen (NY-ESO-1c259) specific T-cell receptor (TCR) and co-expressing a dominant-negative transforming growth factor beta (TGF-β) type II cell surface receptor (dnTGF-ßRII; truncated non-signalling TGF-βRII). The TCR is based on letetresgene autoleucel and specifically recognises a peptide (SLLMWITQC), which is shared by the cancer antigens NY-ESO-1 (CTAG1B) and LAGE-1a (CTAG2) presented on human leukocyte antigen HLA-A*02. The expressed transgene comprises dnTGF-ßRII joined by the foot-and-mouth disease virus ribosome skipping sequence (F2A) to the TCR α chain, joined by the porcine teschovirus-1 ribosome skipping sequence (P2A) to the TCR β chain and is under control of the elongation factor 1 alpha (EF1α) promoter. The construct is flanked by long terminal repeats (LTR) that have a deletion in the U3 part of the LTR, and also contains a ψ packaging signal, Rev response element (RRE), central polypurine tract (cPPT) and a central termination sequence (CTS). The vector is pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein. The leukapheresis material is enriched for CD4/CD8 T lymphocytes by positive immunoselection, activated by CD3 and CD28 agonists and transduced with the lentiviral vector. The cells are then expanded initially in media supplemented with AB serum and interleukin 2 (IL-2), and then in media supplemented with only IL-2. The T lymphocytes (≥95%) are positive for the transgene (≥10% CAR positive), and are cytotoxic to T2 cells loaded with the target peptide

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