Preferred Label : Autologous EGFR-specific CAR-T-Cells Expressing Anti-PD-1/CTLA-4 Antibodies;
NCIt synonyms : Autologous CTLA-4 and PD-1 Antibodies Expressing EGFR-CAR-T Cells; Autologous Anti-CTLA-4/PD-1 Expressing EGFR-CAR-T Cells; Autologous Anti-CTLA-4/PD-1-expressing EGFR-CAR-T; Autologous Anti-PD-1/CTLA4-targeting Antibodies-expressing EGFR-specific CAR-T Cells;
NCIt definition : A preparation of autologous T-lymphocytes that have been activated and genetically
modified to express immune checkpoint antibodies against the negative immunoregulatory
receptors human cell surface receptor programmed cell death protein 1 (PD-1; PDCD1;
CD279) and human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4;
CTLA-4), and are transduced with a gene encoding a chimeric antigen receptor (CAR)
specific for the human tumor-associated antigen (TAA) epidermal growth factor receptor
(EGFR), with potential immunomodulating and antineoplastic activities. After isolation,
activation, transduction, expansion in culture and reintroduction into the patient,
the T-cells in the autologous EGFR specific CAR-T-cells expressing anti-PD-1/CTLA4
antibodies specifically target and kill EGFR-expressing tumor cells. The anti-PD-1
antibody secreted from the CAR-T cells binds to PD-1 expressed on T-cells and prevents
the interaction of PD-1 with its ligand programmed cell death 1 ligand 1 (PD-L1, PD-1L1;
CD274) expressed on cancer cells, which prevents PD-1-mediated signaling and T-cell
exhaustion. The anti-CTLA4 expressed by the CAR-T cells targets and binds to CTLA4
expressed on T-cells, and inhibits the CTLA4-mediated downregulation of T-cell activation.
Both antibodies enhance T-cell activation, improve immunosuppression in the tumor
microenvironment (TME) and improve the T-cell mediated immune response against and
toxicity in EGFR-expressing tumor cells. Both PD-1 and CTLA-4 negatively regulate
T-cell activation and proliferation, and play a key role in immunosuppression within
the TME. EGFR, a receptor tyrosine kinase that is overexpressed in a variety of cancer
cell types, plays a key role in tumor cell proliferation.;
NCI Metathesaurus CUI : CL552497;
Origin ID : C150695;
UMLS CUI : C4725929;
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
