Preferred Label : Autologous PD-1-targeted Chimeric Switch Receptor-modified T Lymphocytes;
NCIt synonyms : Chimeric Switch Receptor PD1CD28 Modified T Cells; Autologous PD-1-targeted CSR T Cells; Autologous Chimeric Switch Receptor PD-1:CD28 Modified T Cells; PD1CD28 CSR T Cells;
NCIt definition : Autologous human T-lymphocytes that are genetically engineered to express a chimeric
switch receptor (CSR) composed of the extracellular ligand binding domain of the human
inhibitory receptor programmed cell death protein 1 (PD-1; PDCD1) fused to the transmembrane
and cytoplasmic co-stimulatory signaling domains of CD28 (PD1CD28; PD-1:CD28 switch
receptor), with potential immunomodulating and antineoplastic activities. Upon reintroduction
of autologous PD-1-targeted CSR-modified T-lymphocytes into the patient, the switch
receptor expressed by the engineered T-cells targets and binds to the PD-1 ligands,
programmed cell death ligand 1 (PD-L1) and 2 (PD-L2) expressed, on tumor cells. The
nature of the PD-1/CD28 switch receptor fusion protein prevents the normal PD1/PD-L1-mediated
T-cell suppression and, instead, promotes signaling through the CD28 domain, which
results in the stimulation of T-lymphocytes. This induces enhanced toxicity against
PD-L1-expressing tumor cells. PD-1 protein, found on activated T-cells, negatively
regulates T-cell activity; it plays a key role in immune evasion and prevents tumor
cell lysis. Exchanging the transmembrane and intracellular domain of PD-1 with that
of CD28 converts PD-L1 into a co-stimulation ligand of primary human CD8 cytotoxic
T-lymphocytes (CTLs). CD28, is a molecule expressed by T-cells that stimulates increased
T-lymphocyte proliferation and activity.;
NCI Metathesaurus CUI : CL520586;
Origin ID : C132251;
UMLS CUI : C4329372;
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
