Виспакабтаген регедлеуцел

Prop. INN (наименование, предложенное ВОЗ)

allogeneic T lymphocytes obtained from peripheral blood mononuclear cells by leukapheresis of healthy donors, electroporated with CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9) hybrid RNA-DNA nucleoprotein complexes to knock out the T cell receptor alpha chain constant (TRAC) and programmed cell death protein 1 (PDCD1) genes and transduced with a recombinant adeno-associated virus vector serotype 6 (AAV6) vector to introduce an anti-CD19 chimeric antigen receptor (CAR) expression cassette at the TRAC locus by homology-directed repair.
The integrated sequence comprises a 5' TRAC homology arm, a protospacer adjacent motif (PAM), the CAR expression cassette, and a 3' TRAC homology arm. The CAR expression cassette consists of an elongation factor alpha (EF-1α) promoter, Kozak sequence, CD8α signal sequence, anti-CD19 single chain variable fragment (scFv clone FMC63), CD8 hinge region, CD8 transmembrane (TM) domain, 4-1BB signaling co-stimulatory domain, CD3ζ signaling domain, and a bovine growth hormone (BGH) polyadenylation sequence.
The leukapheresis material is enriched for CD4/CD8 T lymphocytes by positive immunoselection and subsequently transduced with the vector. Residual TCRαβ+ lymphocytes are removed by magnetic depletion, and the cells are then activated in media containing CD3 and CD28 agonists and interleukin 2 (IL-2). The suspension consists primarily of T lymphocytes (CD45+ and CD4+, CD8+, or CD3+) which are >32% CAR+, have a high proportion PDCD1 knockout cells (average 97%) and are cytotoxic to CD19-expressing cells

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