Preferred Label : Autologous PD-L1/CD80/CD86-targeted CAR-T Cells;
NCIt synonyms : Autologous CAR-T Cells Targeting PD-L1 and CD80/CD86; Zeushield Cytotoxic T Lymphocytes; Zeushield CTLs; Z-CTLs;
NCIt definition : A preparation of autologous human T-lymphocytes engineered to express a chimeric antigen
receptor (CAR) composed of a modified from of the human inhibitory receptor programmed
cell death protein 1 (PD-1; PDCD1), in which the intracellular signal domain of PD-1
is transformed to allow for stimulatory signaling but with an intact extracellular
ligand binding domain that specifically binds the tumor-associated antigen (TAA) programmed
cell death-1 ligand 1 (PD-L1), and a modified form of the T-cell inhibitory receptor
cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), with a transformed intracellular
signal domain to allow for stimulatory signaling, which specifically binds the B7
proteins CD80 (B7-1) and CD86 (B7-2), with potential immunostimulating and antineoplastic
activities. Usually, ligand binding to PD-1 and CTLA-4 inhibits T-cell activity; however,
these modified forms of PD-1 and CTLA-4 promote T-cell stimulatory signaling. Upon
administration, the autologous PD-L1/CD80/CD86-targeted CAR-T cells target and bind
to PD-L1 expressed on certain tumor cells and to CD80/CD86 expressed on antigen-presenting
cells (APCs). This stimulates T-cell activation, T-cell proliferation and enhanced
cytokine production, which induces selective toxicity in tumor cells expressing PD-L1.
PD-1, found on activated T-cells, negatively regulates T-cell activity; it plays a
key role in immune evasion and prevents tumor cell lysis. PD-L1 is often overexpressed
on tumor cell types and plays a key role in immune evasion. The co-stimulatory molecules
CD80 and CD86 play a key role in T-lymphocyte activation upon binding to CD28 upon
antigen recognition; however, binding of CD80 and CD86 to wild-type CTLA-4 inhibits
T-cell activity and results in T-cell exhaustion.;
NCI Metathesaurus CUI : CL550853;
Origin ID : C148216;
UMLS CUI : C4724905;
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
