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drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (CAR γδ T cells)
drug_description
Allogeneic, mRNA-electroporated NKG2D-based CAR-grafted gamma-delta T-cell therapy targeting NKG2D ligands (MICA/B, ULBP1-6) on stressed tumor cells; retains native γδ TCR and DNAM-1 signaling.
nci_thesaurus_concept_id
C167220
nci_thesaurus_definition
A preparation of a subset of allogeneic T-lymphocytes that express only gamma chain and delta chain T-cell receptors (TCRs) and that are engineered to express a chimeric antigen receptor (CAR) encoding for human natural-killer group 2, member D receptor protein (NKG2D or KLRK1; natural killer cell activating receptor group 2D), with potential immunomodulating and antineoplastic activities. Upon administration of the NKG2DL-targeting CAR-grafted gamma delta T cells, these cells specifically target and bind to tumor cells expressing NKG2D ligands (NKG2DL). This induces secretion of pro-inflammatory cytokines and results in the lysis of NKG2DL-expressing tumor cells. In addition, these cells target, bind to and kill NKG2DL-expressing tumor-associated endothelial cells in the neovasculature and immunosuppressive cells, such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) that express NKG2D ligands. Gamma/delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect. Ligands for NKG2D, such as MHC class I chain-related protein A (MICA), MICB, and members of the UL16-binding proteins (ULBP)/retinoic acid early transcript 1 (RAET1) family, are overexpressed on infected cells and most cancer cell types, but are not expressed on most normal, healthy cells.
drug_mesh_term
Chimeric Antigen Receptor T-Cell Immunotherapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Allogeneic gamma-delta T cells engineered by mRNA electroporation to transiently express an NKG2D-based CAR that binds NKG2D ligands (MICA/MICB, ULBP1-6) on stressed tumor and tumor microenvironment cells; engagement activates CAR and native gamma-delta TCR/DNAM-1 signaling to drive pro-inflammatory cytokine release and MHC-independent cytotoxic killing.
drug_name
CTM-N2D
nct_id_drug_ref
NCT05302037