NCI Drug Dictionary

The NCI Drug Dictionary contains technical definitions and synonyms for drugs/agents used to treat patients with cancer or conditions related to cancer. Each drug entry includes links to check for clinical trials listed in NCI's List of Cancer Clinical Trials.

autologous PD-1-targeted chimeric switch receptor-modified T lymphocytes
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. Check for active clinical trials using this agent. (NCI Thesaurus)

Synonym:autologous chimeric switch receptor PD-1:CD28 modified T cells
autologous PD-1-targeted CSR T cells
chimeric switch receptor PD1CD28 modified T cells
PD1CD28 CSR T cells