TGF-beta decoy receptor

A TGF-, β-receptor technology, applied in cytokine/lymphokine/interferon receptors, receptors/cell surface antigens/cell surface determinants, using vectors to introduce foreign genetic material, etc.

Inactive Publication Date: 2020-01-17
特沙公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, long-term maintenance of transferred T cells continues to be limited by their activation status and interactions with host-associated factors
Additionally, overcoming the suppressive nature of the tumor microenvironment remains a major challenge for T cell immunotherapy

Method used

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Embodiment Construction

[0036] The present invention relates to TGF-beta decoy receptors capable of binding and inhibiting TGF-beta-mediated signal transduction, nucleic acids encoding such TGF-beta decoy receptors and cells expressing them. The TGF-β decoy receptor of the present invention functions as a TGF-β decoy receptor. Therapeutic uses of the polypeptides, nucleic acids and cells are also described.

[0037] TGF-β and TGF-β-mediated signaling

[0038] Transforming growth factor beta (TGF-β) is a multifunctional cytokine with three forms, namely TGF-β1, TGF-β2 and TGF-β3. Within the TGF-beta superfamily of cytokines, TGF-beta 1-3 form a subfamily of highly similar proteins.

[0039] Human TGF-β1 (NCBI reference sequence: NP_000651.3) is a protein of 390 amino acids, while TGF-β2 (NCBI reference sequence: NP_001129071.1) is a protein of 442 amino acids, and TGF-β3 (NCBI reference sequence: NP_001316868 .1) Contains 412 amino acids. Each of TGF-β1-3 has at the N-terminus a 20-30 amino acid s...

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Abstract

A TGF-beta decoy receptor comprising a TGF-beta binding region and a lipid anchor region is disclosed. Also disclosed is a chimeric antigen receptor (CAR) comprising a TGF-beta binding region. Also disclosed are compositions comprising, and methods using, the TGF-beta decoy receptors and CARs.

Description

technical field [0001] The present invention relates to decoy receptors for transforming growth factor beta (TGF-beta). Background technique [0002] Immunotherapy with ex vivo expanded or genetically modified T cells shows great promise in the treatment of hematological malignancies. However, the long-term maintenance of transferred T cells continues to be limited by their activation status and interactions with host-associated factors. Additionally, overcoming the suppressive nature of the tumor microenvironment remains a major challenge for T cell immunotherapy. [0003] Transforming growth factor beta (TGF-β) is an immunosuppressive cytokine whose expression is upregulated in a variety of cancers. TGF-β signals through the heterodimeric TGF-β receptor complex, which consists of type 1 and type 2 subunits. Signaling through the TGF-beta receptor has been shown to inhibit T cell proliferation, persistence in vivo and effector function. SUMMARY OF THE INVENTION [000...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/71C07K14/715A61K38/00
CPCA61K38/00C07K14/71C07K14/715A61P35/00A61P35/02A61P43/00C07K14/7151A61K47/544A61K35/17C07K14/7051C12N15/85
Inventor J·康诺利R·霍普金艺杰·P·王S·H·彼得森
Owner 特沙公司
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