autologous NY-ESO-1-redirected CRISPR-edited T cells

{
  "id": "MLC-T-ONC-011726",
  "term": "autologous NY-ESO-1-redirected CRISPR-edited T cells",
  "field": "Oncology and biomedicine",
  "definition": "A preparation of human autologous T lymphocytes that are transduced with a lentiviral vector (LV) encoding a T-cell receptor (TCR) specific for the tumor-associated antigen (TAA) cancer-testis antigen NY-ESO-1 and gene-edited with the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease complex to eliminate endogenous TCR and programmed cell death 1 (PD-1) expression, with potential immunostimulating and antineoplastic activities. The CRISPR guide RNA (gRNA) specifically targets and binds to complementary sites on TCRalpha, TCRbeta and PD-1. In turn, Cas9 cleaves these specific DNA sites, thereby disrupting transcription. Upon isolation, transduction, electroporation with TCRalpha, TCRbeta and PD-1 gRNAs which are complexed to Cas9 RNA to disrupt expression of endogenous TCRalpha, TCRbeta and PD-1, expansion ex vivo, and reintroduction into the patient, the anti-NY-ESO-1 TCR LV-transduced CRISPR-edited autologous T cells recognize and bind to NY-ESO-1-overexpressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of NY-ESO-1-positive tumor cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types, and is not, or is minimally, expressed in normal, healthy cells. PD-1, an immune checkpoint receptor expressed on T cells, plays a key role in tumor immune evasion by binding to its ligand programmed cell death ligand 1 (PD-L1) expressed on tumor cells. By removing PD-1 from T cells, PD-1-mediated signaling is halted which may decrease T-cell exhaustion and may enhance T-cell activity against the NY-ESO-1-expressing tumor cells. Removal of endogenous TCR reduces TCR competition for expression, increases the persistence and function of the expressed transgenic TCR, enhances resistance to T-cell exhaustion and increases T-cell activity.",
  "synonyms": [
    "autologous NY-ESO-1 TCR-expressing CRISPR-edited (TCR and PD-1) T cells",
    "NY-ESO-1-redirected autologous T cells with CRISPR edited endogenous TCR and PD-1",
    "autologous NYCE cells",
    "autologous NYCE T cells",
    "NY-ESO-1-redirected autologous T cells with CRISPR-edited endogenous TCR and PD-1",
    "NY-ESO-1-redirected CRISPR-TCRendo/PD1-edited T cells",
    "NY-ESO-1-redirected CRISPR edited T cells",
    "NY-ESO-1 TCR-PD-1-CRISPR-gene-edited autologous T lymphocytes",
    "autologous NY-ESO-1 transgenic TCR-expressing endogenous TCR-PD-1 gene-edited T cells"
  ],
  "references": [
    "National Cancer Institute Thesaurus"
  ],
  "url": "https://mlchart.com/terminology/oncology/autologous-ny-eso-1-redirected-crispr-edited-t-cells/"
}