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Application of TIGIT immunoadhesin in products for regulating tumor immunity and angiogenesis

A technology of immunoadhesin and angiogenesis, which is applied in the direction of antineoplastic drugs, medical preparations containing active ingredients, peptide/protein components, etc., can solve the problems of less research on TIGIT immunoadhesin, and achieve the expansion of clinical application Prospect and extent, enhanced growth inhibition, enhanced tissue healing effects

Active Publication Date: 2021-01-08
PHARCHOICE THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the study of tumor immunity, there are more studies on the TIGIT protein itself, but less research on the TIGIT immunoadhesin formed by further genetic engineering of the TIGIT protein

Method used

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  • Application of TIGIT immunoadhesin in products for regulating tumor immunity and angiogenesis
  • Application of TIGIT immunoadhesin in products for regulating tumor immunity and angiogenesis
  • Application of TIGIT immunoadhesin in products for regulating tumor immunity and angiogenesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Preparation of TIGIT immunoadhesin

[0030] According to the description in the patent document CN110669139A, TIGIT-Fc-wt and TIGIT-FC-LALA-PG two immunoadhesins were prepared respectively.

Embodiment 2

[0031] Example 2 TIGIT immunoadhesin mediates immune cells to kill tumor cells

[0032] According to the method in the literature [Fu W, et al. Nature communications, 2019, 10(1): 1-12.], assess peripheral blood mononuclear cells (PBMC) in the presence of TIGIT immunoadhesin The killing effect on breast cancer cell line SK-BR-3, lung cancer cell line HCC827, gastric cancer cell line N87, and ovarian cancer cell line SK-OV-3. The ratio of effector cells to target cells was 10:1, the drug concentration was 1 μg / ml, the control IgG was used as a negative control, no drug was added as a blank control, and the cell killing rate was the final cell signal of each treatment group / blank control cell signal. The results are shown in Table 1-4.

[0033] Table 1 The killing effect of PBMC on SK-BR-3

[0034] group Cell killing rate (% blank control) SD P value vs control IgG ControlIgG 10.25 2.45 TIGIT-Fc-wt 72.91 4.37 P＜0.01 TIGIT-FC-LALA-PG 45.65 ...

Embodiment 3

[0082] Example 3 Effect of TIGIT immunoadhesin on internal blood vessels and microcirculation of tumor tissue

[0083] The tumor tissues in the above examples were further subjected to histochemical analysis to detect the perfusion blood vessels in the tissue, and at the same time, the tissue hypoxia level was detected by immunohistochemical method, and the detection method was the same as that in the literature [Hu S, et al. Science translational medicine, 2017, 9(380); Yen W C, et al. Clinical cancer research, 2015, 21(9):2084-2095.]. The results are shown in Table 21-24:

[0084] Table 21 Tissue perfusion blood vessels after the end of SK-BR-3 mouse tumor-bearing model

[0085]

[0086] Table 22 Tissue hypoxia after the end of SK-BR-3 mouse tumor-bearing model

[0087] group Hypoxia signal (% blank control) SD P value vs control IgG Control IgG 105.31 27.35 TIGIT-Fc-wt 10.60 3.20 P＜0.01 TIGIT-FC-LALA-PG 8.17 6.06 P＜0.01

[0...

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Abstract

The invention relates to the technical field of biomedical engineering, and discloses a new application of TIGIT immunoadhesin in products for regulating tumor immunity and angiogenesis, and the experimental results showed that the TIGIT immunoadhesin can effectively enhance the ability of immune cells to kill and recognize tumor cells, enhance the growth inhibition of immune cells on tumor tissues, improve immunosuppression signals in tumor tissues, break the tumor immunosuppression microenvironment, meanwhile, improve the tumor tissue oxygen deficit condition, increase blood flow supply is increased and change the tumor growth environment , so that tumor cells are hammered in two ways. On the other hand, the TIGIT immunoadhesin can stimulate angiogenesis and enhance the healing of new tissues, so that a certain direction is provided for the treatment of vascular injury diseases, and the clinical application prospect and range of the TIGIT immunoadhesin are expanded.

Description

technical field [0001] The invention relates to the technical field of biomedical engineering, in particular to the application of TIGIT immunoadhesin in regulating tumor immunity and regulating angiogenesis products Background technique [0002] TIGIT protein (UniProtKB number: Q495A1) is a member of the poliovirus receptor (PVR) / Nectin family, which consists of an extracellular immunoglobulin variable region (IgV) domain, a type 1 transmembrane domain and a classical immune The intracellular domain composition of the receptor tyrosine inhibitory motif (ITIM) and the immunoglobulin tyrosine tail (ITT) motif can be constructed as a TIGIT immunoadhesive by immunoglobulin Fc fusion technology familiar to those skilled in the art. Attachment. [0003] TIGIT protein has a wide range of uses, and the applicant has applied for two patent applications based on research results: invention patent CN109206523A discloses the preparation of TIGIT immunoadhesin and its use in autoimmune...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K45/06A61P35/00A61P37/04
CPCA61K38/1709A61K45/06A61P35/00A61P37/04A61K2300/00Y02A50/30
Inventor 傅文燕胡适
Owner PHARCHOICE THERAPEUTICS INC
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