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Combined drug composition for breast cancer immunotherapy and application of combined drug composition

A technology of immunotherapy and drug combination, applied in the field of medicine and biology, can solve the problems of limited curative effect and achieve the effect of effective treatment plan

Active Publication Date: 2019-11-19
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, immunotherapy strategies targeting PD-1 have limited efficacy in other solid tumors, such as breast cancer, liver cancer, etc., and there are varying degrees of immunotherapy resistance and recurrence

Method used

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  • Combined drug composition for breast cancer immunotherapy and application of combined drug composition
  • Combined drug composition for breast cancer immunotherapy and application of combined drug composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1: SR1664 inhibits tumor cell proliferation and invasion.

[0055] The purpose of this example is to verify the role of SR1664 inhibitors in malignant transformation of tumor cells. PPARγphosphorylation inhibitor SR1664 has been used as a clinical drug for the treatment of type II diabetes, but its treatment of tumors is still in the research stage. Therefore, SR1664 was selected to verify its possibility as a target for tumor immunotherapy. In vitro experiments showed that SR1664 could significantly inhibit the invasion ability of breast cancer cells ( figure 1 .A, B). The expression of tumor cell proliferation-related genes ANGPT1, CHRNB2, LEP, etc. was detected by QPCR. The results showed that SR1664 inhibitor can significantly inhibit the expression of ANGPT1, CHRNB2, LEP and other genes, and inhibit the proliferation of tumor cells.

Embodiment 2

[0056] Example 2: Combined treatment of PPARγ phosphorylation inhibitor SR1664 and PD-1 blocking antibody inhibits the development of breast cancer in mice.

[0057] In the current tumor immunotherapy methods, PD-1 blocking antibody and CTLA-4 blocking antibody have achieved good therapeutic effects in melanoma and non-small cell lung cancer, but due to the complexity of the tumor microenvironment and the highly immunosuppressive Limiting the effect of tumor immunotherapy. The purpose of this example is to verify the synergistic effect of SR1664 in improving the malignancy of tumor cells and regulating the suppressive characteristics of the immune microenvironment in combination with immune checkpoint blocking antibodies in the process of tumor immunotherapy. The results showed that SR1664 achieved better curative effect in combination therapy with PD-1 blocking antibody, the growth of tumors in mice was significantly slowed down, and the survival time of mice was significantl...

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Abstract

The invention discloses a combined drug composition for breast cancer immunotherapy and an application of the combined drug composition. The combined drug composition comprises an SR1664 inhibitor ineffective quantity and an immunologic test point blocking antibody in effective quantity. The invention further provides a tumor immunotherapy drug combination method. The inventor finds that SR1664 can be used for resisting tumor malignant progression of PPAR gamma phosphorylation mediated with CDK5. The tumor relevant macrophage phenotype and function in tumor microenvironment can be adjusted and controlled, so that the T cellular infiltration is improved, and the immunosuppression tumor microenvironment can be further reversed. Through synergism of the SR1664 and the immunologic test pointblocking antibody, tumor restraining can be further reinforced.

Description

technical field [0001] The invention belongs to the technical field of medicine and biology, and in particular relates to a combined drug combination for immunotherapy of breast cancer and its application. Background technique [0002] Breast cancer has become one of the most common malignant tumors in women all over the world. In recent years, the incidence of breast cancer in my country has been increasing at a rate of 3% per year, becoming the cancer with the fastest-growing mortality rate in cities, and the age of onset is gradually becoming younger. Due to its high heterogeneity, breast cancer is divided into 4 types namely: Luminal A (ER + / PR + Her2 - ), Luminal B (ER + / PR + Her2 + or ER + / PR + Ki67>14%), Her2 + (ER - PR - Her2 + ), and Basal-like type (Triple-negative breast cancer, TNBC) (ER-PR-Her2-). Among them, triple-negative breast cancer (TNBC) refers to breast cancer patients who are negative for estrogen receptor (ER), progesterone receptor ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K39/395A61P35/00
CPCA61K45/06A61K39/395A61P35/00
Inventor 沈萍萍贝云成刘培
Owner NANJING UNIV
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