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A combination drug combination for immunotherapy of breast cancer and its application

A breast cancer and drug technology, applied in the field of medicine and biology, can solve problems such as limited curative effect, achieve effective treatment plan, improve tumor immune microenvironment, and increase infiltration effect

Active Publication Date: 2022-06-07
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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  • A combination drug combination for immunotherapy of breast cancer and its application
  • A combination drug combination for immunotherapy of breast cancer and its application

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 effect of SR1664 inhibitor in malignant transformation of tumor cells. The PPARγ phosphorylation 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 tumor immunotherapy target. In vitro experiments showed that SR1664 could significantly inhibit the invasive 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 could significantly inhibit the expression of ANGPT1, CHRNB2, LEP and other genes, and inhibit the proliferation of tumor cells.

Embodiment 2

[0056] Example 2: PPARγ phosphorylation inhibitor SR1664 combined with PD-1 blocking antibody inhibited the development of breast cancer in mice.

[0057] In the current tumor immunotherapy methods, PD-1 blocking antibodies and CTLA-4 blocking antibodies have achieved good therapeutic effects in melanoma and non-small cell lung cancer, but due to the complexity of the tumor microenvironment and the high degree of immunosuppression limited the effect of tumor immunotherapy. The purpose of this example is to verify the synergistic effect of SR1664 in improving the malignant degree of tumor cells and regulating the inhibitory 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 efficacy in combination therapy with PD-1 blocking antibody, the tumor growth in mice was significantly slowed down, and the survival time of mice was significantly prol...

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Abstract

The invention discloses a drug combination for immunotherapy of breast cancer and application thereof, comprising an effective amount of SR1664 inhibitor and an effective amount of immune checkpoint blocking antibody. The present invention further provides a combination drug method for tumor immunotherapy. The present invention found that SR1664 can act on CDK5-mediated PPARγ phosphorylation to inhibit the malignant progression of tumors, increase T cell infiltration by regulating the phenotype and function of tumor-associated macrophages in the tumor microenvironment, and then reverse the immunosuppressive tumor microenvironment, SR1664 works synergistically with immune checkpoint blocking antibodies to further enhance tumor suppression.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, in particular to a combined drug combination for breast cancer immunotherapy and its application. Background technique [0002] Breast cancer has become one of the most common malignant tumors in women around the world. In recent years, the incidence of breast cancer in my country is increasing at a rate of 3% per year, making it the cancer with the fastest increasing mortality rate in cities. The age of onset is also gradually 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 (Triple-negative breast cancer, TNBC) (ER-PR-Her2-). Among them, triple-negative breast cancer (TNBC) refers to breast cancer patients with negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor ...

Claims

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Application Information

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Patent Type & Authority Patents(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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