Эвонкабтаген пазургедлейцел

Rec. INN (наименование, зарегистрированное ВОЗ)

allogeneic T cells obtained from peripheral blood by leukapheresis, genetically modified by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) mediated gene editing consisting of two guide RNAs (gRNAs) introduced transiently as CAS9-gRNA ribonucleoprotein (RNP) complex for the targeted disruption of the T cell receptor alpha chain constant (TRAC) and β2 microglobulin (B2M) loci and insertion of an anti-CD19 chimeric antigen receptor (CAR) transgene into the TRAC locus via an adenoassociated virus serotype 6 (AAV6) vector. The CAR is composed of a humanized single-chain variable fragment (scFv) derived from the murine antibody FMC63 targeting CD19, followed by a CD8 hinge and transmembrane region, a CD28 co-stimulatory domain and a CD3ζ signalling domain. Expression of the CAR is driven by the elongation factor 1 alpha (EF-1α) promoter and is terminated by a synthetic polyadenylation sequence. The CD19 expression cassette is flanked by two TRAC homology arms guiding the expression cassette to the TRAC locus. The T cells are cultured in the presence of growth medium containing interleukin 2 (IL-2) and 7 (IL-7) and are ≥30% CAR+ T cells, ≤0.5% TCR+ and ≤30% B2M+.

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