Preferred Label : Anti-CD71/vcMMAE Probody-drug Conjugate CX-2029;
NCIt synonyms : PBC CX-2029; Antibody Prodrug-drug Conjugate CX-2029; CD71-Directed Probody Therapeutic CX-2029; PDC-targeting CD71 CX-2029; CD71-directed PDC CX-2029; Anti-CD71 Probody/vcMMAE Drug Conjugate CX-2029;
NCIt definition : A probody-drug conjugate (PDC) composed of a monoclonal antibody directed against
the transferrin receptor 1 (TFR1;TRP1; CD71), linked to a proprietary masking peptide
that covers the active antigen-binding site of the antibody through a protease-cleavable
linker, and conjugated, via a valine-citrulline (VC) peptide linker, to the potent
cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity.
Upon administration of the anti-CD71/vcMMAE PDC CX-2029, the anti-CD71 moiety is unable
to bind to CD71 antigen, which is highly expressed on both tumor and healthy dividing
cells, until the masking peptide that is attached to the anti-CD71 probody is cleaved
by tumor-associated proteases upon extravasation into the tumor microenvironment (TME).
Local protease-mediated removal of the linker and masking peptide enables specific
binding of the unmasked anti-CD71 moiety to CD71 expressed on tumor cells. Upon internalization
and proteolytic cleavage, MMAE is released into the cytosol of CD71-expressing tumor
cells, binds to tubulin, and inhibits microtubule polymerization, which induces both
G2/M phase arrest and tumor cell apoptosis. CD71, a transmembrane glycoprotein, is
a highly expressed protein present in a number of solid and hematologic cancers, but
is also expressed on normal, healthy tissues. The peptide masking of CX-2029 minimizes
binding of the anti-CD71 antibody moiety to normal, healthy cells and may minimize
systemic toxicity, when compared to other anti-CD71 antibody-drug conjugates (ADCs).
Tumor-associated proteases are present in high concentrations and aberrantly activated
in the TME.;
Molecule name : CX 2029; CX-2029;
NCI Metathesaurus CUI : CL554515;
Origin ID : C153287;
UMLS CUI : C4727145;
Semantic type(s)
- UMLS correspondences (same concept)
- CX-2029 [MeSH Supplementary Concept]
- concept_is_in_subset
- has_target
