Preferred Label : Anti-HER2/CD3/XTEN Protease-activated T-cell Engager AMX-818;
NCIt synonyms : XTENylated Protease-activated T Cell Engager AMX-818; TCE AMX-818; HER2-XPAT AMX-818; Prodrug TCE AMX-818; Prodrug HER2-XPAT T-cell Engager AMX-818; Xtenylated Protease-activated TCE AMX-818; Masked HER2 TCE AMX-818;
NCIt definition : A protease-activated prodrug T-cell engager (TCE) composed of two tandem single chain
variable fragments (scFvs) targeting the tumor-associated antigen (TAA) human epidermal
growth factor receptor 2 (EGFR2; HER2; ErbB2) and CD3, a T-cell surface antigen, and
conjugated, via a protease-cleavable linker, to two unstructured polypeptides (XTEN),
with potential immunomodulating and antineoplastic activities. Double XTEN masking
allows for universal masks that sterically hinder target binding of AMX-818 until
cleaved by proteases; it also prolongs half-life. Upon intravenous administration
of anti-HER2/CD3/XTEN protease-activated TCE AMX-818, the XTEN masks are proteolytically
cleaved in the tumor microenvironment (TME) by dysregulated proteases at the base
of the XTEN masks which releases the active TCE. The anti-HER2 scFv moiety targets
and binds to HER2 expressed on tumor cells. The CD3 scFv moiety targets and binds
to T-cells. The resulting cross-linkage may trigger a potent cytotoxic T-lymphocyte
(CTL) response against HER2-expressing tumor cells. HER2, a receptor tyrosine kinase
(RTK) mutated or overexpressed in many tumor cell types, plays a key role in tumor
cell proliferation and tumor vascularization. The XTEN masks allows specific activation
of AMX-818 in the TME and limits systemic unmasking; this minimizes systemic toxicity
and increases efficacy. In healthy tissues, where protease activity is tightly regulated,
the HER2-XTENylated protease-activated T cell engager (XPAT) AMX-818 remains predominantly
inactive.;
Molecule name : AMX 818; AMX-818;
NCI Metathesaurus CUI : CL1792372;
Origin ID : C187696;
UMLS CUI : C5706437;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
