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Application of anti-S100A4 antibody in injury of anti-CD137 antibody-mediated antitumor immunity

A technology of S100A4 and CD137, which is applied in the direction of anti-tumor drugs, anti-animal/human immunoglobulins, antibodies, etc., can solve problems such as immune damage, achieve small side effects, and reduce liver toxicity

Inactive Publication Date: 2017-11-24
BEIJING DOINGTIMES INST OF TRANSLATIONAL MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the improvement of immunity may cause different degrees of side effects, that is, causing immune damage

Method used

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  • Application of anti-S100A4 antibody in injury of anti-CD137 antibody-mediated antitumor immunity
  • Application of anti-S100A4 antibody in injury of anti-CD137 antibody-mediated antitumor immunity
  • Application of anti-S100A4 antibody in injury of anti-CD137 antibody-mediated antitumor immunity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1: Anti-tumor effect of anti-CD137 monoclonal antibody simultaneously causes severe liver damage

Embodiment 2

[0043] Example 2: Anti-CD137 monoclonal antibody treatment induces large amounts of S100A4 + Infiltration of macrophages ( figure 2 )

[0044] Embodiment: (1) anti-CD137 monoclonal antibody and RatIg process mouse ( figure 2 A): 6-week-old male wild-type C57BL / 6 mice were intraperitoneally injected with 100 μg of anti-CD137 monoclonal antibody or RatIg once a week for 5 weeks. Liver tissues were harvested at designated time points at 1, 3, and 5 weeks for further observation. (2) Liver section staining and collagen deposition and S100A4 + Cell Quantitative Analysis ( figure 2 B-2D): 7 μm thick frozen liver tissue sections were prepared. After routine processing, the liver sections were stained with H&E or saturated picric acid containing 0.1% Sirius red and 0.1% Fast Green for the detection of collagen deposition; the frozen Liver sections were incubated with anti-S100A4 (Abcam, Cambridge, UK) antibody followed by staining with AlexaFluor 488 or 555-conjugated secondar...

Embodiment 3

[0045] Example 3: S100A4 + Cell-selective deletion attenuates anti-CD137 monoclonal antibody-induced liver injury and liver fibrosis ( image 3 )

[0046] Embodiment: (1) Establishment of mouse model: S100A4 will be selectively deleted + Cellular S100A4-TK mice (Eric G. Nielsen, Northwestern University, Feinberg College of Medicine) were given intraperitoneal injections of 100 μg anti-CD137 monoclonal antibody on the first day of each week, and on the first, third, and third days of each week. 50mg / kg GCV (ganciclovir, Ganciclovir) (Hubei Keyi Pharmaceutical Co., Ltd., China) or intraperitoneal injection of PBS were given on the 4th, 6th and 7th days, and the treatment was repeated for 4 weeks. (2) Mouse liver section staining: S100A4-TK mouse liver sections treated with anti-CD137 monoclonal antibody were labeled with S100A4 (Abcam, Cambridge, UK) and Ki67 (proliferating cell-associated nuclear antigen) to mark cells in the proliferation cycle ) antibody for staining ( i...

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Abstract

The invention discloses application of anti-S100A4 antibody in injury of anti-CD137 antibody-mediated antitumor immunity. The application has the advantage that when the tumor is treated by the CD137 antibody, the serious liver toxicity caused by anti-CD137 co-stimulated antibody is avoided or greatly relieved by at least one of S100A4 antibody, matter causing lack of S100A4 in human body, and matter capable of deleting S100A4 positive macrophage in the human body.

Description

technical field [0001] The invention relates to the field of immunotherapy, in particular to the application of anti-S100A4 antibody in anti-CD137 antibody-mediated anti-tumor immune injury. Background technique [0002] In recent years, cancer immunotherapy has received widespread attention and rapid development. They are different from traditional radiotherapy, chemotherapy and surgery. They aim to stimulate the patient's immune system and kill tumors with the help of the immune system. However, the improvement of immunity may cause different degrees of side effects, that is, immune damage. These immune impairments are sometimes severe and even fatal. For example, it is reflected in (1) skin rash and irritation of mucous membranes: toxicity to the skin, rash and skin itching; (2) diarrhea and colitis; (3) liver toxicity; (4) hypofunction of the pituitary gland, adrenal gland, and thyroid gland . [0003] The co-stimulatory molecule CD137 (also known as 4-1BB and TNFRSF9...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00A61P37/02
CPCA61K2039/507C07K16/18C07K16/2878
Inventor 秦志海张金华宋坤王俊李亚男刘双庆戴成亮陈列平王盛典
Owner BEIJING DOINGTIMES INST OF TRANSLATIONAL MEDICINE
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