Application of combination of CD47 antibody and IL-6 cytokine drug to tumor treatment and method for verifying tumor treatment by combination of CD47 antibody and IL-6 cytokine drug

A technology of cytokines and IL-6, applied in the medical field, can solve the problems of IL-6 cytokines and CD47 antibodies that have not yet been seen, and achieve the effect of simplifying the dosage

Active Publication Date: 2020-11-10
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] There is no report on the combination of IL-6 cytokine and CD47 antibody for anti-tumor

Method used

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  • Application of combination of CD47 antibody and IL-6 cytokine drug to tumor treatment and method for verifying tumor treatment by combination of CD47 antibody and IL-6 cytokine drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] In vitro macrophage phagocytosis detection of CD47 antibody alone and CD47 antibody combined with IL-6 cytokine drug or IL-6 cytokine drug loaded on nanomaterials

[0027] S1. Obtaining and culturing macrophages in vitro; in this embodiment, bone marrow was taken from mouse leg bones, and macrophages were cultured in vitro. And take the macrophages to 24-well plate for overnight culture, and each well 5 × 10 4 a macrophage.

[0028] S2. In vitro detection of macrophage phagocytosis of colon cancer cells based on CD47 antibody, CD47 antibody combined with IL-6 cytokine drug, and CD47 antibody combined with IL-6 cytokine drug loaded on nanomaterials.

[0029] In this example, first replace the culture medium of macrophages with serum-free medium, 2 Incubate for 2 hours in the incubator;

[0030] Take another 2×10 5 A colon cancer cell line (MC38) was washed with PBS solution, stained with CFSE, and then 10ug / ml IgG or CD47 antibody was added according to the treatment...

Embodiment 2

[0035] CD47 antibody alone and CD47 antibody combined with IL-6 cytokine drug or IL-6 cytokine drug loaded on nanomaterials in the treatment of colon cancer in RAG-1KO mouse subcutaneous xenograft tumor model

[0036] S1. The colon cancer cell line was subcutaneously transplanted into the right side of RAG-1KO mice to construct a transplanted tumor model. In this embodiment, 5×10 5 A colon cancer cell line (MC38) was subcutaneously transplanted into the right side of RAG-1KO mice.

[0037] S2. Based on the transplanted tumor model, compare the therapeutic effect of CD47 antibody alone, CD47 antibody combined with IL-6 cytokine drug on colon cancer. The CD47 antibody combined with IL-6 cytokine drug includes CD47 antibody combined with IL-6 loaded on nanomaterials Cytokine drugs. In this example, the mice were divided into eight different treatment groups, with 5 mice in each treatment group, and the eight treatment groups were injected with IgG+PBS, anti-CD47+PBS, IgG+IL-6, ...

Embodiment 3

[0044] CD47 antibody alone and CD47 antibody combined with IL-6 cytokine drug or IL-6 cytokine drug loaded on nanomaterials in the treatment of colon cancer in C57BL / 6 mouse subcutaneous xenograft tumor model

[0045] S1. The colon cancer cell line was subcutaneously transplanted into the right side of a C57BL / 6 mouse to construct a transplanted tumor model. In this example, 1×10 6 A colon cancer cell line (MC38) was subcutaneously transplanted into the right side of C57BL / 6 mice.

[0046] S2. Comparing the therapeutic effect of CD47 antibody, CD47 antibody combined with IL-6 cytokine drug on colon cancer based on transplanted tumor model, the CD47 antibody combined with IL-6 cytokine drug includes CD47 antibody combined with IL-6 cells loaded on nanomaterials Factor medicine. In this example, the mice were divided into eight different treatment groups, with 5 mice in each treatment group, and the eight treatment groups were injected with IgG+PBS, anti-CD47+PBS, IgG+IL-6, an...

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Abstract

The invention relates to an application of combination of a CD47 antibody and an IL-6 cytokine drug to tumor treatment and a method for verifying tumor treatment by combination of the CD47 antibody and the IL-6 cytokine drug. IL- 6 is used for coordination of positive effect of an immune system and the CD47 antibody to tumor treatment, macrophages are fully activated to kill tumor cells, and the immunotherapy effect is improved. Immune response of the tumor cells can be further achieved on the basis of IL-6 activated T cells and the like, the response rate of combined application for tumor treatment is increased, the anti-tumor effect of an organism immune system is fully activated, and compared with other methods such as chemotherapy, adverse reactions can be remarkably reduced. In addition, the IL-6 cytokine drug is loaded by a nano material with a tumor or tumor microenvironment targeting function, so that the treatment targeting property can be improved, the IL-6 is enriched in thetumor microenvironment, the quantity of the IL-6 entering peripheral blood is reduced, the side effect is reduced, the quantity of the CD47 antibody reaching the tumors can be fully exerted, the dosage of the CD47 antibody independently acting on the tumors is reduced, and complete combined application is realized.

Description

technical field [0001] The present invention relates to the medical field, and more specifically, relates to an application of CD47 antibody combined with IL-6 cytokine drug in tumor treatment and a method for verifying the treatment of tumor. Background technique [0002] CD47 is also known as integrin-related protein, and its ligand is the signal regulatory protein α chain (SIRPα) on the surface of macrophages. When CD47 binds to SIRPα, it can transmit inhibitory signals and inhibit the phagocytic activity of macrophages. Tumor cells express CD47 and combine with macrophage SIRPα to promote tumor cell immune escape, so that a large number of macrophages cannot fully exert their phagocytosis, reducing the impact of macrophages on tumor development. On this basis, in order to achieve the purpose of treating tumors, targeted research in the prior art includes drugs that block the CD47-SIRPα pathway and target CD47, including CD47 antibodies, but most of the indications of the...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K38/20A61K31/4418A61K31/7048A61K45/06A61K9/00A61P35/00G01N33/68
CPCA61K39/39558A61K38/204A61K31/4418A61K31/7048A61K45/06A61K9/0087A61P35/00G01N33/6872G01N2333/70503A61K2300/00
Inventor 陈俊钟诚黄春柳许小丁李森林王立翔王馨语毛承舟李懿逸
Owner SUN YAT SEN UNIV
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