Preferred Label : Bifunctional TGF-beta Antagonist/IL-15 Protein Complex HCW9218;
NCIt synonyms : TGF-beta Trap/IL-15 Protein Complex HCW9218; Fusion Protein Complex HCW9218; Bifunctional Molecule HCW9218; Fusion Protein HCW9218;
NCIt definition : A heterodimeric, bifunctional fusion protein composed of the ectodomains of the transforming
growth factor (TGF) beta (TGF-beta; TGFb) receptor II (TGFbRII;TGFBR2) fused to a
human immunostimulatory cytokine interleukin-15 (IL-15)/ IL-15 receptor alpha complex,
with potential immunostimulatory and antineoplastic activities. Upon administration
of the bifunctional TGF-beta antagonist/IL-15 protein complex HCW9218, the TGFbRII
moiety specifically and selectively targets, binds to and neutralizes TGF-beta, an
immunosuppressive cytokine secreted by tumors. This prevents TGF-beta from binding
to TGF receptors and prevents TGFb-mediated signaling. This abrogates TGFb-mediated
immunosuppression in the tumor microenvironment (TME), enhances immune cell infiltration
and anti-tumor immunity in the TME, and promotes a cytotoxic T-lymphocyte (CTL)-mediated
immune response against tumor cells leading to tumor cell death. This may lead to
a reduction in TGFb-dependent proliferation of cancer cells. The IL-15 moiety stimulates
the proliferation and cytotoxic activity of natural killer (NK) cells, cytotoxic T-lymphocytes
(CTLs) and memory T-cells locally in the TME, which further induces an anti-tumor
immune response, and increases tumor cell killing. In addition, by stimulating the
immune system and NK cell activation, HCW9218 may eliminate chemotherapy-induced senescent
cells in tumors and normal tissues, may reduce senescence-associated secretory phenotype
(SASP) factor activity, and may reduce therapy-induced senescence (TIS)-mediated proinflammatory
side effects in normal tissues. TGFb, overproduced in many types of cancer, plays
a key role in immunosuppression in the TME, enhances tumor cell proliferation, and
promotes cancer progression. IL-15 regulates CD8 T and NK cell development, activation
and proliferation.;
Molecule name : HCW-9218; HCW 9218;
NCI Metathesaurus CUI : CL1779106;
Origin ID : C186737;
UMLS CUI : C5667085;
Semantic type(s)
- concept_is_in_subset
- has_target
