Preferred Label : Engineered Toxin Body Targeting CTLA-4 MT-8421;
NCIt synonyms : Anti-CTLA-4 ETB MT-8421; ETB MT-8421; ETB Targeting CTLA-4 MT-8421; Anti-CTLA-4 Engineered Toxin Body MT-8421;
NCIt definition : An engineered toxin body (ETB) composed of biparatopic heavy chain variable domains
(VHHs) targeting the human T-cell-expressed receptor cytotoxic T-lymphocyte-associated
antigen 4 (CTLA-4; CTLA4; CD152), fused to the enzymatically active, de-immunized,
ribosome-inactivating cytotoxic payload Shiga-like toxin-A subunit (SLTA), with potential
immune checkpoint inhibitory and antineoplastic activities. Upon administration of
ETB targeting CTLA-4 MT-8421, the antibody fragments specifically target and bind
to two non-overlapping epitopes on CTLA-4-expressing T regulatory cells (Tregs) in
the tumor microenvironment (TME). Upon internalization, the SLTA moiety is released
and acts as an N-glycosidase, which binds to and cleaves an adenine nucleobase in
the 28S RNA component of the 60S subunit of ribosomes and prevents ribosome activity.
This inhibits protein synthesis and leads to apoptosis in CTLA-4-expressing Tregs
in the TME. The depletion of the immune suppressive Tregs in the TME may enhance a
cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA-4,
an inhibitory receptor and member of the immunoglobulin superfamily (IgSF), is overexpressed
by Tregs in the TME and plays a key role in the downregulation of the immune system.;
Molecule name : MT 8421; MT-8421;
NCI Metathesaurus CUI : CL1920781;
Origin ID : C201568;
UMLS CUI : C5907909;
Semantic type(s)
- concept_is_in_subset
- has_target
