Anti-tgf-beta receptor ii antibodies

A β-receptor and antibody technology, applied in the medical field, can solve the problems of reducing collagen deposition and liver function, which have not yet been disclosed

Inactive Publication Date: 2014-07-30
IMCLONE SYSTEMS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] So far, no highly specific, high-affinity anti-TGFβRII antibody has been disclosed, and such an antibody is therefore needed: specifically binds the extracellular domain of human TGFβRII with very high affinity, blocks human Combination of TGFβ1, TGFβ2 and TGFβ3 with human TGFβRII, inhibition of angiogenesis, inhibition of tumor cell growth, inhibition of migration and invasion of cancer cells, reduction of collagen deposition and liver function, inhibition of ligand-induced T cell regulation, or combined cytotoxic agent inhibition tumor growth

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[0088] Materials and Cell Lines

[0089] Human TGFβ1, TGFβ2 and TGFβ3 can be produced recombinantly and purified or can be purchased from, eg, R&D Systems. Recombinant TGFβRII Fc fusion protein (TGFβRII-Fc) and soluble recombinant TGFβRII alkaline phosphatase (TGFβRII-AP) protein can be expressed in stably transfected cells and obtained from cell culture supernatants according to procedures known to those skilled in the art. Liquid purification (Tessler, J. Biol. Chem., 269:12456-12461 (1994)).

[0090] Human cancer cell lines BXPC-3, PANC-1, MDA-MB-231 and mouse tumor cell lines EMT6, 4T1, CT26, B16-F10 and myeloma cell line P3-X63-Ag8.653 are available from American Type Culture American Type Tissue Culture Collection (Manassas, VA). The MDA-MB-231 luciferase transfected cell line is available from Sunnybrook Health Sciences Centre. Cells can be maintained in RPMI1640 or IMDM medium (Invitrogen / Life Technologies, Inc., Rockville, MD) containing 10% fetal calf serum (FCS, ...

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Abstract

The present invention relates to antibodies against human transforming growth factor beta receptor II (TGFβRII), pharmaceutical compositions comprising the antibodies and methods of using the antibodies alone or in combination, for example for the treatment of cancer and fibrosis.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to: antibodies binding to human transforming growth factor beta receptor II (TGFβRII), pharmaceutical compositions comprising the antibodies, and methods of using the antibodies, for example for the treatment of cancer, fibrosis and fibrotic disease. Background technique [0002] TGFβ is a pleiotropic cytokine that regulates cell growth and differentiation, motility, extracellular matrix production, and immune function. TGF[beta] has three mammalian isoforms, TGF[beta]-1, TGF[beta]-2 and TGF[beta]-3, each with distinct in vivo functions. All 3 TGFβs use the same receptor signaling system. Binding of TGFβ to TGFβRII is a key step in the initiation of activation of the TGFβ signaling pathway, which leads to phosphorylation of Smad2 and translocation of the activated Smad2 / Smad4 complex to the nucleus to regulate gene expression. [0003] JP2004 / 121001A disclosed that with high affin...

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/28A61K39/395A61P35/00
CPCA61K39/39558C07K2317/565C07K2317/76C07K2317/21C07K2317/73C07K2316/96A61K2039/505C07K16/2863C07K2317/56C07K2317/92A61P35/00A61P43/00A61K2300/00C07K16/28A61K39/395
Inventor 吴嫣
Owner IMCLONE SYSTEMS
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