Арлокабтаген аутолейцел

Prop. INN (наименование, предложенное ВОЗ)

USAN (наименование, принятое к употреблению в США)

autologous T lymphocytes obtained from peripheral blood mononuclear cells (PBMCs) by leukapheresis, transduced with a self-inactivating, non-replicating lentiviral vector encoding a chimeric antigen receptor (CAR) targeting G protein-coupled receptor, class C group 5 member D (GPRC5D). The expressed transgene comprises a human CD33 leader sequence, a human GPRC5D-specific single chain variable fragment (scFv) binding domain (clone ET150-8), an IgG4 hinge region, CD28 transmembrane domain, 4-1BB co-stimulatory domain and CD3ζ signalling domain, under control of a hybrid human elongation factor 1 alpha (EF-1α) promoter / human T-cell leukemia virus type 1 (HTLV-1) R enhancer. The construct is flanked by 5' and 3' long terminal repeats (LTRs) and also contains a ψ packaging signal, partial gag, a Rev response element (RRE), a Flap structure and a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The vector is pseudotyped with the vesicular stomatitis virus (VSV) G envelope protein.
The PBMCs are enriched for CD8+ and CD4+ T lymphocytes, which are subsequently cultured together, activated with a magnetic-based CD3/CD28 activation reagent, and then transduced with the lentiviral vector encoding the GPRC5D- specific CAR. The cells are expanded in serum-free media containing interleukin-2, interleukin-7 and interleukin-15 to obtain the necessary number of CD3+ CAR+ cells and then harvested.
The cells are ≥80% CD3+, with ≥10% CAR+. The cells respond to GPRC5D-expressing target cells by producing an array of pro- inflammatory cytokines and demonstrate cytotoxicity against the target tumour cells

Поделиться этой страницей