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Application of SEMA4C in preparation of antitumor drugs

A technology for expressing products and cells, which is applied in the field of biomedicine and can solve problems such as ineffective treatment

Pending Publication Date: 2021-05-28
TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH +1
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

Although anti-PD-1 / PD-L1 combined with paclitaxel chemotherapy has a good therapeutic effect, anti-immune checkpoint therapy with single anti-PD-1 / PD-L1 has little effect

Method used

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  • Application of SEMA4C in preparation of antitumor drugs
  • Application of SEMA4C in preparation of antitumor drugs
  • Application of SEMA4C in preparation of antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0032] The experimental method that the present invention relates to:

[0033] 1. Animal experiments

[0034] Female huPBMC-NOG-dKO humanized mice of the same age and similar body weight were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. 5×10 6 MDA-MB-231 breast cancer cells were resuspended in serum-free DMEM medium, mixed with Matrigel 1:1 and inoculated subcutaneously in mice. When the volume of the tumor reaches 50-100mm 3 , the mice were randomly divided into control group, anti-SEMA4C group and anti-PD-L1 group. Intraperitoneal injection of 200 μg drug was given twice a week, and the tumor volume of the mice was measured every day and the change curve was drawn. All mice were sacrificed on Day 28, the subcutaneous tumor tissue was completely stripped, and the weight of each tumor was weighed for statistical analysis.

[0035] 2. Cell culture

[0036] Human breast cancer cell line MDA-MB-231 was obtained from ATCC and cultured using D...

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of SEMA4C in preparation of antitumor drugs. Based on research on breast cancer, SEMA4C with high breast cancer tissue specificity expression is found, and the SEMA4C with high expression participates in tumor metastasis invasion and tumor proliferation related to lymphatic vessel formation of breast cancer. However, the development of neutralizing antibodies in the aspects of immunoregulation, participation in anti-tumor reaction and medicines has not been studied and reported. According to the application, the interaction mode of SEMA4C and T cells is proved, a neutralizing antibody capable of blocking combination of SEMA4C and T cells is screened out, and an in-vitro co-culture experiment result shows that anti-SEMA4C can recover chemotactic and anti-tumor functions of the T cells; and in-vivo experiments find that anti-SEMA4C can significantly inhibit tumor growth, and the tumor inhibition effect is obviously better than that of anti-PD-1, which indicates that the SEMA4C neutralizing antibody has great potential in the anti-tumor aspect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of SEMA4C in the preparation of antitumor drugs. Background technique [0002] Tumor tissue is a complex ecological microenvironment, including a variety of cells (tumor cells, fibroblasts, lymphocytes, etc.) and soluble molecules, as well as an acidic, hypoxic, and hypertensive physical environment. Although CD8+ T cells, NK cells and NKT cells have direct tumor killing function in tumor tissues, CD4+ T cells can secrete anti-tumor cytokines and promote the activation of CD8+ T cell functions through antigen-presenting cells (APCs) to inhibit tumors. , but there are complex immunosuppressive molecules and mechanisms in the tumor microenvironment that mediate tumor cells to escape the attack of immune cells, such as: low oxygen and low pH environment; immunosuppressive cytokines IL-10, TGF-β; low glucose and Important amino acids; regulatory T cel...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K45/00A61P35/00
CPCA61K48/005A61K45/00A61P35/00
Inventor 高庆蕾马丁夏宇王思媛黄璞方田
Owner TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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