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Application of combination of clostridium ghonii and tumor angiogenesis inhibitor

A technology of tumor angiogenesis and Clostridium gordii, which is applied in the field of oncology, can solve the problems of changing the tumor immunosuppressive microenvironment, achieve the effect of improving the immune microenvironment, high targeting, and enhancing anti-tumor efficacy

Pending Publication Date: 2021-12-31
SHANDONG XINCHUANG BIOLOGICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, there are currently no relevant reports that Clostridium gordoi combined with tumor angiogenesis inhibitors can significantly change the tumor immunosuppressive microenvironment and enhance the anti-tumor effect

Method used

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  • Application of combination of clostridium ghonii and tumor angiogenesis inhibitor
  • Application of combination of clostridium ghonii and tumor angiogenesis inhibitor
  • Application of combination of clostridium ghonii and tumor angiogenesis inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Materials and methods

[0041] Clostridium gordii spore freeze-dried powder

[0042] Clostridium gordii spore freeze-dried powder for injection, the strain is MW-DCG-LCv-26 strain, which is preserved in the Australian National Metrology Institute, strain preservation number V12 / 001486, batch number: 202003001-1, Shandong Xinchuang Biotechnology Ltd. developed. Clostridium gordii spore freeze-dried powder for injection uses Clostridium gordii spores as the active ingredient and 1% sucrose as the excipient, after -40°C for 4h; -35°C for 10min while vacuuming; , -20°C 26h, -15°C 2h, -10°C 10min, -5°C 10min, 0°C 10min, 10°C 2h, 15°C 10min, 20°C 3h, 27°C 3h freeze-drying procedures, the specification is 1×10 8 CFU / tube; reference substance freeze-dried powder, batch number: 201910002F, developed by Shandong Xinchuang Biotechnology Co., Ltd., prepared with 1mL 1% sucrose solution through the above freeze-drying procedure; 0.9% sodium chloride injection, batch number: 200506...

Embodiment 2

[0073] High safety and strong targeting of Clostridium gordii in solid tumor models

[0074] model building

[0075] Establish colon cancer subcutaneous xenograft model. Establishment of middle cerebral artery occlusion (MCAO) model in SD rats. Establishment of acute myocardial infarction (MI) model in C57BL / 6 mice.

[0076] animal grouping

[0077] On the day of screening tumor-bearing animals, select tumor volume 0.35 ~ 0.60cm 3 Experimental animals are used for experiments. According to the random principle, the screened animals that meet the requirements were divided into 4 groups by lottery: intravenous administration control group, intratumoral administration control group, intravenous administration of Clostridium gordoi spore group, intratumoral administration of Clostridium gordoi spore group , 8 mice per group.

[0078] SD rat middle cerebral artery occlusion (MCAO) model was randomly divided into 4 groups, healthy rat control group, cerebral infarction model c...

Embodiment 3

[0095] Antitumor effect of Clostridium gordii spores combined with different doses of Etan in CT26 mouse model

[0096] According to the random principle, mice meeting the requirements (tumor volume 0.31-0.41cm 3 ) were divided into 8 groups by lottery: control group, Clostridium gordoi spore group, high-dose Aitan group, middle-dose Aitan group, low-dose Aitan group, low-dose Bacillus combined with Aitan group, spores combined with Aitan medium Dose group, spore combined with Aitan high-dose group.

[0097] Control group: intratumoral administration of the same volume of 0.9% sodium chloride injection;

[0098] Clostridium gordii spore group: the dose is 1×10 7 cfu / tumor / time, intratumoral administration, 2 times of administration;

[0099] Aitan high-dose group: the dose is 180mg / kg / d, intragastric administration, once a day, 7 times in total;

[0100] Aitan medium dose group: the dose is 120mg / kg / d, intragastric administration, once a day, 7 times in total;

[0101] Ai...

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Abstract

The invention relates to an application of a combination of clostridium ghonii and a tumor angiogenesis inhibitor in cancer treatment. It is found for the first time that the combination of clostridium ghonii and the low-dose tumor angiogenesis inhibitor reduces infiltration of M2-like macrophages, MDSC and the like in tumors, reduces the number of TGF beta in the tumors and reduces the inhibition effect of anti-tumor immune response in TME. Meanwhile, by combining with the low-dose tumor angiogenesis inhibitor, immune cells such as CD8 < + >, CD3 < + > T and F4 / 80 < + > can be promoted to infiltrate into tumors, the immune microenvironment in the tumors is improved, and the anti-tumor curative effect is enhanced. The application can be applied to advanced malignant solid tumor types, the TME is converted into an immune activation state from an immunosuppression state by combining the clostridium ghonii with low-dose apatinib to reduce the anti-tumor immune response inhibition effect in the TME, and efficient anti-tumor is achieved.

Description

technical field [0001] The present invention relates to the application of Clostridium gordii combined with tumor angiogenesis inhibitors, in particular to the application of using Clostridium gordii combined with tumor angiogenesis inhibitors to relieve the tumor immunosuppressive microenvironment, improve the tumor microenvironment and enhance the effect of treating tumors, which belongs to tumor field of technology. Background technique [0002] Tumor microenvironment (Tumor microenvironment, TME) is a local homeostatic environment composed of tumor cells, stromal cells, extracellular matrix, and biomolecules infiltrated in the process of tumor growth. TME provides the necessary material basis for tumor occurrence, development, and invasion, and regulates various biological behaviors such as tumor metastasis and recurrence. At the same time, TME increases tumor drug resistance and radiation resistance, reducing the therapeutic effect. The immune regulation in the TME pl...

Claims

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Application Information

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IPC IPC(8): A61K35/742A61K45/06A61P35/00
CPCA61K35/742A61K45/06A61P35/00A61K2300/00A61K39/3955A61K2039/505A61K2039/52C07K16/2863C12R2001/145C12N1/205A61K39/08A61K31/444
Inventor 王勇刘园园王少鹏朱红王丹邢立超徐兴鲁牛卉果双双韩停姜圣彪杨冬霞郜玉霞邵石丽李晓楠郑嘉辉张蓉
Owner SHANDONG XINCHUANG BIOLOGICAL TECH CO LTD
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