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Application of poly inosinic acid cytidine monophosphate combined with anti-CD47 antibody in tumor treatment

An anti-tumor drug and antibody technology, applied in the medical field, can solve the problems that macrophages cannot fully exert their phagocytosis, reduce the influence of macrophages, and the treatment effect is not obvious, so as to promote innate immune function, improve treatment effect, and improve The effect of tumor treatment effect

Inactive Publication Date: 2020-10-30
SUN YAT SEN UNIV
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  • Description
  • Claims
  • Application Information

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Problems solved by technology

Tumor cells express CD47 and combine with macrophage SIRPα to promote immune escape, so that a large number of macrophages cannot fully exert their phagocytosis, thereby 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, such as anti-CD47 antibodies, but their therapeutic effects are limited, and they have certain effects on cancers of the hematopoietic system. , but the therapeutic effect on solid tumors is not obvious, and the response rate in the treatment of cancers including solid tumors is low
At the same time, although CD47 antagonists such as anti-CD47 antibodies in the prior art have certain curative effects in the treatment of some cancers, they will also cause more adverse reactions at the same time, because in addition to tumor cells, normal cells such as red blood cells also express CD47. CD47 antagonists will also act on normal cells and cause relatively strong adverse reactions

Method used

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  • Application of poly inosinic acid cytidine monophosphate combined with anti-CD47 antibody in tumor treatment

Examples

Experimental program
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Effect test

Embodiment 1

[0020] Combination of polyinosinic acid (Poly I:C) and anti-CD47 antibody in the treatment of colon cancer in a xenograft model

[0021] S1. Cultivate and obtain the colon cancer cell line to be inoculated; in this embodiment, the colorectal cancer cell line MC38 is cultured, and when the density grows to 80%-90%, a cell suspension of 106 / 50 μL is prepared;

[0022]S2. Modeling and grouping of transplanted tumor models; in this embodiment, 18 healthy male C57BL / 6 mice of the same age were selected, and the mice were between 8 and 10 weeks old, and were divided into three groups, including the control group, Anti-CD-47 antibody treatment group, Poly I:C + anti-CD-47 antibody combined treatment group. The cell suspension obtained in step S1 was subcutaneously inoculated on the right sides of all mice in the three groups, and each mouse was inoculated with 50 μl (10 6 MC38 colorectal cancer cells). Specifically, the inoculation in this embodiment is by intraperitoneal injection....

Embodiment 2

[0028] Combination of polyinosinic acid (Poly I:C) and anti-CD47 antibody in the treatment of AOM / DSS autologously induced colon cancer

[0029] S1. Cultivate and obtain the colon cancer cell line to be inoculated; in this embodiment, the colorectal cancer cell line MC38 is cultured, and when the density grows to 80%-90%, a cell suspension of 106 / 50 μL is prepared;

[0030] S2. Modeling and grouping of autologous induced tumor mouse models; in this example, 18 healthy male C57BL / 6 mice of the same age were selected, and the mice were between 8 and 10 weeks old, and were divided into three groups, including Control group, anti-CD-47 antibody treatment group, PolyI:C + anti-CD-47 antibody combined treatment group. and adopt figure 1 During the modeling process, AOM 8mg / kg was firstly injected into all mice in the three groups, and then the mice were cultivated, and 2.5% DSSWater was injected every day in the second week, the fifth week, and the eighth week, and the rest During...

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Abstract

The invention discloses an application of polyinosinic acid combined with an anti-CD47 antibody in tumor treatment, which can promote the innate immune function of macrophages so as to improve the activation performance of the anti-CD47 antibody, promote the macrophages to kill tumor cells and improve the response rate of tumor patients to the anti-CD47 antibody. Meanwhile, when the polyinosinic acid is combined with the anti-CD47 antibody to treat tumors, adverse reactions such as anemia and the like caused in the treatment process can be remarkably reduced, and the life quality of a patientand the compliance in the treatment process are improved; more importantly, solid tumors including colon cancer can be treated by combining the Poly I: C immunologic adjuvant with the anti-CD47 antibody for immunotherapy, so that the restriction that the anti-CD47 antibody is difficult to realize an effective treatment effect on the solid tumors in the prior art is broken through; a new research direction is provided for immunotherapy and colon cancer treatment in the prior art, and development of the field of tumor treatment is promoted.

Description

technical field [0001] The present invention relates to the medical field, and more specifically, relates to the application of polyinosinic acid cytidylic acid combined with anti-CD47 antibody in tumor treatment. 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 immune escape, so that a large number of macrophages cannot fully exert their phagocytosis, thereby 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, such as anti-CD47 antibodies, but their therapeutic effects are limited, and they have certain effects on canc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61K39/395A61P35/00
CPCA61K39/39A61K39/3955A61P35/00A61K2039/55583
Inventor 陈俊黄春柳何伟玲王颖钊毛承舟钟诚王馨语李懿逸王立翔李嘉琪
Owner SUN YAT SEN UNIV
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