Preferred Label : CRISPR-Cas9-mediated PD-1 and TCR Gene-deleted Anti-mesothelin CAR T-cells;
NCIt synonyms : CRISPR-Cas9-mediated Anti-mesothelin CAR T-cells; CRISPR-Cas9-mediated Gene-edited Anti-mesothelin CAR-T Cells; Anti-mesothelin CAR-transduced CRISPR-Cas9-edited T-cells; CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells;
NCIt definition : A preparation of human T-lymphocytes transduced with a chimeric antigen receptor (CAR)
specific for the tumor-associated antigen (TAA) mesothelin and gene-edited with the
clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease complex
to eliminate endogenous TCR and programmed death 1 (PD-1; PDCD1; CD279; programmed
cell death-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 introduction into the patient,
the CRISPR-Cas9-mediated PD-1 and TCR gene-deleted anti-mesothelin CAR T-cells recognize
and bind to mesothelin-overexpressing tumor cells. This may result in a specific cytotoxic
T-lymphocyte (CTL)-mediated killing of mesothelin-positive tumor 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 death ligand 1 (PD-L1; cluster of differentiation
274; CD274; programmed cell death-1 ligand 1) 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 mesothelin-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. Mesothelin is upregulated on a variety of tumor cell
types.;
NCI Metathesaurus CUI : CL938075;
Origin ID : C158606;
UMLS CUI : C4764291;
Semantic type(s)
- Cell [UMLS semantic type]
- concept_is_in_subset
