Preferred Label : Autologous NY-ESO-1-redirected CRISPR-edited T Cells;
NCIt synonyms : NY-ESO-1-redirected CRISPR-TCRendo/PD1-edited T Cells; Autologous NYCE T-cells; Autologous NY-ESO-1 Transgenic TCR-expressing Endogenous TCR-PD-1 Gene-edited T-cells; NY-ESO-1 TCR-PD-1-CRISPR-gene-edited Autologous T-lymphocytes; NY-ESO-1-redirected CRISPR Edited T Cells; Autologous NYCE T Cells; 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; NY-ESO-1-redirected Autologous T Cells with CRISPR Edited Endogenous TCR and PD-1;
NCIt 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.;
NCI Metathesaurus CUI : CL555289;
Origin ID : C154288;
UMLS CUI : C4727561;
Semantic type(s)
- Cell [UMLS semantic type]
- chemical_or_drug_affects_cell_type_or_tissue
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
