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- Bc3b8f55ce4e7bc92f39d59fafe8c746b NCIT_P378 "NCI" @default.
- Bc3b8f55ce4e7bc92f39d59fafe8c746b type Axiom @default.
- Bc3b8f55ce4e7bc92f39d59fafe8c746b annotatedProperty IAO_0000115 @default.
- Bc3b8f55ce4e7bc92f39d59fafe8c746b annotatedSource NCIT_C185164 @default.
- Bc3b8f55ce4e7bc92f39d59fafe8c746b annotatedTarget "A tri-specific, designed ankyrin repeat proteins (DARPin)-based agent targeting the tumor-associated protein fibroblast activation protein (FAP), CD40 receptor and human serum albumin (HSA), with potential immunostimulatory and antineoplastic activities. Upon administration, FAP/CD40-targeting DARPin MP0317 targets and binds to both FAP, localized predominantly on cancer-associated fibroblasts (CAFs) in the tumor stroma, and CD40, a cell surface stimulatory receptor expressed on various immune cells including B-lymphocytes, monocytes and dendritic cells (DCs). The simultaneous binding to FAP and CD40 results in local clustering of FAP-expressing tumor stromal cells and CD40-expressing immune cells. Activation of CD40 induces proliferation and activation of B-lymphocytes, shifts the induction of suppressive macrophages towards immunostimulatory macrophages, activates monocyte-derived DCs (moDCs), and leads to the secretion of inflammatory cytokines, which activates the immune system to induce the proliferation and activation of cytotoxic T-lymphocytes (CTLs) against tumor cells. CD40, a member of the tumor necrosis factor receptor superfamily (TNFRSF), plays a key role in the activation of the immune system. FAP is abundantly expressed by CAFs in the majority of solid tumors. HSA binding prolongs the half-life of MP0317. Compared to antibodies, DARPins are small in size, have favorable pharmacokinetics and allow for both high affinity binding and efficacy." @default.