FDA official logo
GSRS logoPFDA official logo

TEOTRESGENE AUTOGELEUCEL

UNII:X95LED7WZP
Type:INGREDIENT SUBSTANCE
Formula:
Preferred Substance Name:TEOTRESGENE AUTOGELEUCEL
GSRS Full Record:
X95LED7WZP
i

  • Teotresgene Autogeleucel
  • autologous T lymphocytes obtained from peripheral blood via leukapheresis, electroporated with three CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) /guide RNA (gRNA) nucleoprotein complexes to disrupt the T cell receptor alpha chain constant (TRAC), T cell receptor beta constant (TRBC) 1 and 2, and TGF-beta receptor type-2 (TGFBR2) loci. At the same time, the cells are electroporated with linear, closed-end, double-stranded DNA (lc-dsDNA), encoding an HLA-C*08:02-restricted T cell receptor (TCR) targeting K-Ras variant G12D, which leads to site-specific integration of the dsDNA at the TRAC locus via homologous recombination. The TCR transgene consists of TCRβ and TCR α chains separated by self-cleaving 2A peptide sequences and by a modified dihydrofolate reductase (DHFR). The apheresis material is enriched via immunomagnetic selection of CD4 and CD8 expressing cells and activated using anti-CD3 and anti-CD28 antibodies in growth media containing recombinant cytokines interleukin 7 (IL-7) and IL-15. The cells are then electroporated with the constructs before further expansion in media containing IL-7 and IL-15. During culture, the cells also undergo an enrichment of transgene positive T lymphocytes via chemoselection with methotrexate (MTX). The T lymphocytes (sum of CD4 + plus CD8 + ≥80%) are enriched for CD8 + cells, with subsets of T helper lymphocytes (CD4 + ). The CD4 + subset is predominately composed of CD27 + CD28 + and CD45RA -CCR7 - populations, whereas the CD8+ subset is a mixture of CD27 + CD28 + , CD45RA - CCR7 - , CD45RA + CCR7 - , and CD45RA + CD62L + populations. The transgene (neoantigen-specific TCR) expression in the final substance is ≥40%, and the knock-out efficiencies for TRAC, TRBC and TGFBR2 are measured by digital PCR. Following co-culture of the T lymphocytes with tumor target cell lines the lymphocytes proliferate, are cytotoxic and secrete interferon gamma (IFN-γ) and IL-2 in response to antigen stimulation
  • teotresgene autogeleucel [INN]




UNII - X95LED7WZP | UNII Search Service