Preferred Label : Anti-EGFR/anti-CD3 Tumor Protease-activated T-cell Engager JANX008;
NCIt synonyms : EGFR-targeted Tumor-activated T Cell Engager JANX008; EGFR-TRACTr JANX008; EGFR-targeted TRACTr JANX008; Double-masked Tumor Activated T Cell Engager JANX008; Double Masked EGFR TCE JANX008; Anti-EGFR/Anti-CD3 Protease-activated TCE JANX008; Anti-EGFR/CD3 Protease-activated TCE JANX008;
NCIt definition : A protease-activated, double masked tumor activated T-cell engager (TCE) composed
of a tumor-associated antigen (TAA) binding domain that targets epidermal growth factor
receptor (EGFR) and a T-cell binding domain that targets CD3, that are both conjugated,
via a tumor protease-cleavable linker, to a peptide mask that prevents binding of
the EGFR-binding domain to EGFR-expressing tumor cells and binding of the CD3-binding
domain to T-cells, respectively, and an albumin-binding domain that extends circulating
half-life, with potential immunomodulating and antineoplastic activities. Upon intravenous
administration of anti-EGFR/anti-CD3 tumor protease-activated TCE JANX008, the tumor
protease-cleavable linkers are proteolytically cleaved in the tumor microenvironment
(TME), which separates both the EGFR-binding domain and the CD3-binding domain of
JANX008 from their respective peptide masks, thereby allowing the binding domains
to bind to their respective targets. The EGFR-binding domain targets and binds to
EGFR expressed on tumor cells. The CD3-binding domain targets and binds to T-cells.
The resulting cross-linkage triggers a cytotoxic T-lymphocyte (CTL) response against
EGFR-expressing tumor cells in the TME. EGFR, a receptor tyrosine kinase, is overexpressed
on the surfaces of various tumor cell types. The albumin-binding domain, which is
attached to the CD3-binding domain mask, binds to albumin in the circulation, thereby
extending the half-life of JANX008. While in circulation, the two tumor protease-cleavable
peptide masks inhibit EGFR and CD3 binding and may prevent cytokine release syndrome
(CRS) and on-target EGFR healthy tissue toxicity while increasing its efficacy when
activated in the TME.;
Molecule name : JANX-008; JANX 008;
NCI Metathesaurus CUI : CL1906925;
Origin ID : C199574;
UMLS CUI : C5854428;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
