Preferred Label : Dalutrafusp Alfa;
NCIt synonyms : Bispecific Antibody GS-1423;
NCIt definition : A bifunctional fusion protein composed of a humanized aglycosylated immunoglobulin
G1 kappa (IgG1k) antibody directed against the ectoenzyme 5'-ecto-nucleotidase (cluster
of differentiation 73; CD73; 5'-NT; ecto-5'-nucleotidase; NT5E), fused to the extracellular
domain of human transforming growth factor beta (TGFbeta) receptor type II (TGFbetaRII),
with potential immunomodulating and antineoplastic activities. Upon administration,
dalutrafusp alfa targets and binds to both CD73 expressed on tumor cells and TGFbeta
in the tumor microenvironment (TME). The binding of dalutrafusp alfa to CD73 prevents
CD73-mediated conversion of extracellular adenosine monophosphate (AMP) to adenosine
and the adenosine-mediated suppression of lymphocyte activity and trafficking. This
increases the activity of cytotoxic T-lymphocytes (CTLs), activates macrophages and
reduces the activity of both myeloid-derived suppressor cells (MDSCs) and regulatory
T-lymphocytes (Tregs). By abrogating the inhibitory effect on the immune system and
enhancing the CTL-mediated immune response against cancer cells, tumor cell growth
is decreased. The binding of dalutrafusp alfa to TGFbeta neutralizes TGFbeta and prevents
TGFbeta-mediated signaling. This abrogates TGFbeta-mediated immunosuppression in the
TME, enhances immune cell infiltration and anti-tumor immunity in the TME, and promotes
the CTL-mediated immune response against tumor cells leading to tumor cell death.
CD73, a plasma membrane protein belonging to the 5'-nucleotidase (NTase) family, is
upregulated on a number of cancer cell types and catalyzes the conversion of extracellular
nucleotides, such as AMP, to membrane-permeable nucleosides, such as adenosine; it
plays a key role in adenosine-mediated immunosuppression within the TME. TGFbeta,
overproduced in many types of cancer, plays a key role in immunosuppression in the
TME, enhances tumor cell proliferation, and promotes cancer progression.;
UNII : KNL22F1WCK;
CAS number : 2419918-89-9;
Molecule name : GS-1423; GS 1423; AGEN-1423; AGEN 1423;
NCI Metathesaurus CUI : CL972431;
Origin ID : C167206;
UMLS CUI : C5706660;
Semantic type(s)
- concept_is_in_subset
- has_target
