drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
Immune-stimulating antibody conjugate (ISAC) comprising a trastuzumab-biosimilar monoclonal antibody linked via a non-cleavable, cell-impermeable linker to a TLR7/8 agonist; binds HER2 on tumor cells to localize TLR7/8 activation and trigger innate and adaptive anti-tumor immunity.
nci_thesaurus_concept_id
C172388
nci_thesaurus_preferred_term
Trastuzumab Imbotolimod
nci_thesaurus_definition
An immune stimulating antibody conjugate (ISAC) consisting of trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, conjugated to a Toll-like receptor (TLR) 7/8 dual agonist, with potential immunostimulating and antineoplastic activities. Upon administration of trastuzumab imbotolimod, the trastuzumab moiety targets and binds to HER2 expressed on tumor cells and, simultaneously, the TLR 7/8 dual agonist moiety targets, binds to and activates TLR7/8 expressed on antigen-presenting cells (APCs), specifically dendritic cells (DCs), in the tumor microenvironment (TME). The trastuzumab binding to the tumor cells causes the engulfment of the trastuzumab imbotolimod-bound tumor cells by tumor-associated myeloid (TAM) cells and the TAMs travel to the lymph nodes. The DCs activated by the TLR7/8 agonist causes the activation of TLR7/8-mediated pathways, and stimulates the maturation and activation of DCs, thereby re-activating the immune system against the tumor cells. Activation of DCs results in the production of pro-inflammatory cytokines, and the activation of cytotoxic T-lymphocyte (CTL)- and B-lymphocyte-mediated immune responses against tumor-associated antigens (TAAs), which lead to tumor cell lysis. TLR7 and 8, members of the TLR family, play fundamental roles in the activation of the innate immune system, myeloid cell responses and tumor antigen presentation. HER2 is overexpressed by a variety of tumor cell types.
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
Immune-stimulating antibody conjugate: a trastuzumab-biosimilar mAb targets HER2 on tumor cells to localize a linked TLR7/8 agonist to the tumor microenvironment, activating TLR7/8 on dendritic and other antigen-presenting cells. This triggers innate immune activation, pro-inflammatory cytokine production, enhanced antigen presentation, and subsequent cytotoxic T-cell and B-cell responses leading to anti-tumor activity.
drug_name
BDC-1001
nct_id_drug_ref
NCT05954143