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Recombinant fusion protein TIGIT-Fc and application in resisting transplant rejection thereof

A technology of fusion protein and transplant rejection, which is applied in the field of biomedicine and can solve the problems that patients do not achieve the desired therapeutic effect

Active Publication Date: 2018-09-21
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Abstract
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  • Claims
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Problems solved by technology

However, in practical applications, a considerable proportion of patients still do not achieve the desired therapeutic effect, suggesting that more in-depth research is still needed to explore more co-stimulatory molecular regulation mechanisms

Method used

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  • Recombinant fusion protein TIGIT-Fc and application in resisting transplant rejection thereof
  • Recombinant fusion protein TIGIT-Fc and application in resisting transplant rejection thereof
  • Recombinant fusion protein TIGIT-Fc and application in resisting transplant rejection thereof

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Embodiment Construction

[0027] In the present invention, the full-length sequence of TIGIT is first cloned in mouse cells, and the sequence of the extracellular region of the cell membrane is inserted into the eukaryotic expression vector pSectag2-Fc by using bioinformatics analysis, and the sequence of the fusion gene is determined by gene sequencing; collected after transfection into CHO cells Cell culture supernatant, using anti-Fc affinity chromatography to purify TIGIT-Fc recombinant fusion protein; detect the effect of TIGIT-Fc recombinant fusion protein on macrophage polarization in macrophage culture in vitro and LPS stimulation model; The effect of TIGIT-Fc pretreatment of macrophages on the proliferation and differentiation of T cells was detected. Establish C57 / BL6-Balb / c mouse model of allograft vascularized skin flap transplantation, observe the regulation of TIGIT-Fc on allograft rejection; detect host Treg ratio, macrophage polarization, and lymphocyte response to donor or Reactivity t...

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Abstract

The invention provides a recombinant fusion protein TIGIT-Fc and application in resisting transplant rejection thereof. The linear tandem polypeptide is capable of inducing specific T cell response toexert an immunoprotective effect. The amino acid sequence of the recombinant fusion protein TIGIT-Fc is shown in SEQ ID NO: 1. The nucleotide sequence for encoding the recombinant fusion protein TIGIT-Fc is shown in SEQ. ID. NO: 2. The recombinant fusion protein TIGIT-Fc can effectively regulate macrophage polarization by interfering CD226 / TIGIT-CD155 signaling pathways, which is conducive to theinduction of allograft tolerance.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to a recombinant fusion protein TIGIT-Fc and its application in anti-transplant rejection. Background technique [0002] Organ transplantation is an important and even the only treatment to save the life and improve the quality of life of patients with end-stage organ failure. Since the 1980s, the field of organ transplantation has developed rapidly. Tissues such as kidney, heart, liver, pancreas and islets, parathyroid gland, lung, bone marrow, and cornea are commonly used solid transplant organs. Kidney transplantation in developed countries has become The preferred conventional therapy for benign end-stage renal disease, surgical operation is no longer the main problem restricting the development of organ transplantation. [0003] Thanks to the advancement of medical technology and the widespread use of broad-spectrum immunosuppressive drugs, graft failure within the first y...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62A61K38/17A61K47/68A61P37/06
CPCA61K38/00C07K14/705
Inventor 庄然张圆张栋梁谢建刚胡伟张赟方亮李琦金伯泉
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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