Мотакабтаген луревгедлейцел

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 the insertion of an anti-B cell maturation antigen (BCMA) CAR transgene into the TRAC locus via an adeno-associated virus serotype 6 (AAV6) vector. The CAR is composed of a humanized single-chain variable fragment (scFv) targeting BCMA, followed by a CD8 hinge and transmembrane region, a 4-1BB (CD137) costimulatory domain and a CD3ζ signalling domain. Expression of the CAR is driven by the elongation factor, EF-1α, promoter and is terminated by a synthetic poly A sequence. The BCMA 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, ≤0.4% TCR+ and ≤30% B2M+.

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