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AMSOKIGENE AUTOLEUCEL

UNII:SDW528DU9W
Type:INGREDIENT SUBSTANCE
Formula:
Preferred Substance Name:AMSOKIGENE AUTOLEUCEL
GSRS Full Record:
SDW528DU9W
i

  • Amsokigene Autoleucel
  • amsokigene autoleucel [INN]
  • autologous tumour-infiltrating lymphocytes (TILs) derived from patient tumour tissue such as melanoma or non-small cell lung cancer, transduced with a self-inactivating (SIN) gamma-retroviral vector encoding a fusion protein comprised of interleukin-15 (IL-15) fused to the C-terminal part of human CD80 that ensures membrane tethering of IL-15 via the CD80 transmembrane domain, separated by a GS linker from a human carbonic anhydrase 2 derived drug (acetazolamide) responsive domain (mbIL15-CA2DRD). The transgene is preceded by an immunoglobulin kappa light chain leader sequence and is under control of a retroviral MP71 promoter derived from a fragment of the myeloproliferative sarcoma virus U3 promoter, and the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE; viral X-protein deleted). The vector also contains the Moloney murine leukemia virus (MMLV) psi packaging sequence, the MMLV psi+ region, and is flanked by 5' and 3' long terminal repeats (LTRs). The vector is pseudotyped with the Gibbon ape leukemia virus (GALV) envelope glycoprotein. The lymphocytes are mechanically isolated from resected tumour biopsies and culture expanded using a two-step protocol consisting of a cell expansion in medium supplemented with human AB serum, recombinant human interleukin 2 (rhIL-2), anti-CD3 antibody (muromonab-CD3) and anti-4-1BB antibody (urelumab). The cells are then activated with anti-CD3 prior to transduction with the gamma-retroviral vector. Following transduction, the cells are further cultured in the presence of irradiated feeder cells supplemented with human AB serum and acetazolamide. The final cell substance is primarily comprised of CD3+ T lymphocytes (≥80%) predominantly of CD8+ lineage, and ≥30% of cells express the IL-15 transgene. The CD8+ T lymphocytes generally consist of ≥90% effector memory T cells, <10% central memory and terminally differentiated effector memory T cells. The T-lymphocytes demonstrate interferon gamma (IFN-γ) release modulated by acetazolamide after CD3/CD28 bead stimulation




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