Dimer immunoadhesin, pharmaceutical composition and application thereof
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A technology of immunoadhesin and receptor, which is applied in the field of related diseases, and can solve the problems such as unclear therapeutic value of immunoadhesin
Pending Publication Date: 2020-01-10
PHARCHOICE THERAPEUTICS INC
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[0006] However, in recurrent miscarriage, the imbalance of maternal-fetal immune factors is also a key link in the pathological progress of the disease (Trowsdale J, Betz AG. Nat Immunol.2006; 7:241-6.), but due to the particularity of intrauterine maternal-fetal immunity , the therapeutic value of these immunoadhesins is unclear
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Embodiment 1
[0040] Example 1. Construction and expression of soluble dimeric immunoadhesin
[0041] Such as figure 1 As shown, the soluble dimeric immunoadhesin is a dimer with antibody IgG Fc, and the method of constructing and expressing the dimeric immunoadhesin itself is a routine experimental technique in the field, and a brief description is as follows:
[0042] (1) Whole gene synthesis of soluble dimeric immunoadhesin TIGIT-Fc-wt (comprising two polypeptide chains, the amino acid sequence and nucleotide sequence of each polypeptide chain are shown in SEQ ID NO: 2 and SEQ ID NO: 9 shown); TIGIT-Fc-LALA-PG (comprising two polypeptide chains, the amino acid sequence and nucleotide sequence of each polypeptide chain are shown in SEQ ID NO:3 and SEQ ID NO:10); TIGIT / CTLA4-Fc (comprising two polypeptide chains, the amino acid sequence and nucleotide sequence of the first polypeptide chain are shown in SEQ ID NO: 5 and SEQ ID NO: 11, and the amino acid sequence and nucleotide sequence of...
Embodiment 2
[0045] Embodiment 2.Biacore analysis
[0046] According to the literature (Bruhns P. et al. Blood, 2009, 113(16): 3716-3725.), BiacoreT100 (GE Healthcare) was used to detect the affinity of each immunoadhesin. The specific detection affinity values are shown in Table 1.
[0049] Example 3. Effects of Dimeric Immunoadhesins on Decidual Immune Cells
[0050] Dendritic cells DC (CD1c positive) were isolated from decidual tissue of human pregnancy terminated for non-medical reasons. The DC cells were divided into negative control group (control IgG, 10 μg / ml), dimer immunoadhesin treatment group (dimer immunoadhesin, 10 μg / ml), LPS treatment group (100 ng / ml mL), 48 hours later, the levels of interleukin 10 (IL-10) and tumor necrosis factor α (TNFα) were detected, and the detection method was the same as that in the literature (Guo PF, et al. Blood, 2010, 116(12): 2061-2069.).
[0051] Test results such as figure 2 As shown, it was shown that dimeric immunoadhesin can significantly increase IL-10 secretion level without increasing TNFα level, confirming that dimeric immunoadhesin can exert immune tolerance through DC.
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Abstract
The invention relates to the technical field of biomedical engineering, and provides a composition related to soluble dimeric immunoadherend and a method thereof. The dimeric immunoadhesin comprises afirst dimerized polypeptide chain and a second dimerized polypeptide chain. Wherein a structural general formula of the first polypeptide chain is Z1-Z2, and the structural general formula of the second polypeptide chain is Y1-Y2. Wherein Z1 is (i) an extracellular domain of a first cell surface receptor or a functional variant or fragment thereof, or (ii) a first cytokine or a functional variantor fragment thereof; Z2 is an immunoglobulin constant region dimerization domain or a functional variant or fragment thereof. Y1 is an extracellular domain or a functional variant or fragment thereofof a second cell surface receptor, or (ii) a second cytokine or a functional variant or fragment thereof. Y2 is an immunoglobulin constant region dimerization domain or the functional variant or fragment thereof. The dimer protein can be used for treating and preventing diseases related to infertility.
Description
technical field [0001] The invention relates to the technical field of biomedical engineering, in particular to a dimer immunoadhesin, a pharmaceutical composition using it as an active component and its medical application, especially the application for treating infertility and other related diseases . Background technique [0002] There are many important membrane molecules on the surface of T cells, which play an important role in the activation, proliferation, differentiation and effector function of T cells. According to different functions, it can be mainly divided into the following categories: (1) TCR-CD3 complex, which enables T cells to recognize the antigen peptide-MHC molecular complex on the antigen-presenting cell and transmit activation signals to the cell; (2) ) CD4 molecule and CD8 molecule: respectively assist TCR of CD4+ and CD8+ T cells to recognize antigens and participate in the transduction of T cell activation signals; (3) co-stimulatory molecules: ...
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