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drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy
drug_description
Autologous, gene-modified CAR-T cell therapy targeting Claudin 18.2 (CLDN18.2); administered as a single infusion to mediate T-cell cytotoxicity against CLDN18.2-positive tumors.
nci_thesaurus_concept_id
C174192
nci_thesaurus_preferred_term
Anti-CD47 Monoclonal Antibody IMC-002
nci_thesaurus_definition
A human immunoglobulin G4 (IgG4) monoclonal antibody targeting leukocyte surface antigen CD47, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-CD47 monoclonal antibody IMC-002 targets and binds to CD47 expressed on tumor cells, blocking the interaction of CD47 with signal regulatory protein alpha (SIRPa) expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of macrophage activation and phagocytosis of cancer cells. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1), which is expressed on macrophages, and results in macrophage activation and the specific phagocytosis of tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSCs) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, thereby allowing cancer cells to proliferate. IMC-002 does not bind to red blood cells (RBCs). This may prevent adverse effects such as anemia that can result from the blockade of CD47 expressed on RBCs.
drug_mesh_term
Chimeric Antigen Receptor T-Cell Therapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Autologous T cells are engineered ex vivo to express a chimeric antigen receptor specific for Claudin 18.2 (CLDN18.2). Upon binding CLDN18.2 on tumor cells, CAR signaling (CD3zeta with costimulatory domains) activates T-cell proliferation, cytokine release, and perforin/granzyme-mediated cytotoxicity, enabling targeted killing of CLDN18.2-positive tumors after a single infusion.
drug_name
IMC002
nct_id_drug_ref
NCT05946226