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- NCIT_C186737 IAO_0000115 "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." @default.
- NCIT_C186737 NCIT_A7 NCIT_C128303 @default.
- NCIT_C186737 NCIT_A7 NCIT_C20455 @default.
- NCIT_C186737 NCIT_NHC0 "C186737" @default.
- NCIT_C186737 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C186737 NCIT_P108 "Bifunctional TGF-beta Antagonist/IL-15 Protein Complex HCW9218" @default.
- NCIT_C186737 NCIT_P208 "CL1779106" @default.
- NCIT_C186737 NCIT_P322 "GDC" @default.
- NCIT_C186737 NCIT_P399 "809416" @default.
- NCIT_C186737 normalizedInformationContent "100" @default.
- NCIT_C186737 referenceCount "1" @default.
- NCIT_C186737 hasExactSynonym "Bifunctional Molecule HCW9218" @default.
- NCIT_C186737 hasExactSynonym "Bifunctional TGF-beta Antagonist/IL-15 Protein Complex HCW9218" @default.
- NCIT_C186737 hasExactSynonym "Fusion Protein Complex HCW9218" @default.
- NCIT_C186737 hasExactSynonym "Fusion Protein HCW9218" @default.
- NCIT_C186737 hasExactSynonym "HCW 9218" @default.
- NCIT_C186737 hasExactSynonym "HCW-9218" @default.
- NCIT_C186737 hasExactSynonym "HCW9218" @default.
- NCIT_C186737 hasExactSynonym "TGF-beta Trap/IL-15 Protein Complex HCW9218" @default.
- NCIT_C186737 inSubset NCIT_C128784 @default.
- NCIT_C186737 inSubset NCIT_C157711 @default.
- NCIT_C186737 inSubset NCIT_C157712 @default.
- NCIT_C186737 inSubset NCIT_C176424 @default.
- NCIT_C186737 type Class @default.
- NCIT_C186737 isDefinedBy ncit.owl @default.
- NCIT_C186737 label "Bifunctional TGF-beta Antagonist/IL-15 Protein Complex HCW9218" @default.
- NCIT_C186737 subClassOf NCIT_C129820 @default.
- NCIT_C186737 subClassOf NCIT_C129821 @default.
- NCIT_C186737 subClassOf NCIT_C186737 @default.
- NCIT_C186737 subClassOf NCIT_C1908 @default.
- NCIT_C186737 subClassOf NCIT_C1909 @default.
- NCIT_C186737 subClassOf NCIT_C274 @default.
- NCIT_C186737 subClassOf NCIT_C307 @default.
- NCIT_C186737 subClassOf NCIT_C308 @default.