Мацитегтаген аутолейцел

Prop. INN (наименование, предложенное ВОЗ)

autologous CD4/CD8 enriched T lymphocytes derived from peripheral blood mononuclear cells (PBMC) of patients by leukapheresis, transduced with a self- inactivating, non-replicating lentiviral vector encoding a a chimeric antigen receptor (CAR) targeting the intercellular adhesion molecule-1 (ICAM-1) fused to human somatostatin receptor type 2 (SSTR2), under control of the human elongation factor-1 alpha (EF-1α) promoter. A self-cleaving P2A peptide sequence separates the two transgenes.
, The CAR transgene comprises a CD8α signal peptide, a c-Myc tag, the I domain of the lymphocyte function- associated antigen 1 (LFA-1, also known as integrin alpha-L, a natural ICAM-1 ligand) with an F292A mutation, a CD8α/CD28 hinge and transmembrane domain, a 4-1BB costimulatory domain and a CD3ζ signalling domain. The somatostatin receptor type 2 (SSTR2) is used to bind 68Ga-DOTA-TATE for visualization of the CAR T lymphocytes via positron emission tomography-computed tomography (PET-CT).
, The transgene construct is flanked by 5' and 3' long terminal repeats (LTRs) and also contains a ψ packaging signal, a truncated gag, a Rev response element (RRE), a central polypurine tract (cPPT) sequence, a Woodchuck hepatitis virus post- transcriptional regulatory element (WPRE) and a qPCR synthetic ID tag sequence.
, 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 in media supplemented with serum replacement and interleukin 2 (IL-2) and 7 (IL-7). The cell suspension consists of T lymphocytes (≥90%) with greater than 10% of the T lymphocytes expressing the transgene. The lymphocytes secrete interferon gamma (IFN-γ) and exhibit cytotoxic activity in response to culture with target tumor cells