CN-122005527-A - Application of gamma-aminobutyric acid in preparation of synergist of immune checkpoint inhibitor

CN122005527ACN 122005527 ACN122005527 ACN 122005527ACN-122005527-A

Abstract

The invention discloses an application of gamma-aminobutyric acid in preparing a synergist of an immune checkpoint inhibitor, belonging to the technical field of tumor treatment. Compared with single treatment, the combined administration of GABA and immune checkpoint inhibitor can remarkably inhibit tumor growth and increase the infiltration proportion of CD8 + T cells in tumor tissues, and simultaneously increase the proportion of IFN-gamma + 、TNF-α + and Perforin + CD8 + T cells, so that the cytotoxicity function of the T cells is enhanced. The results show that GABA can promote the anti-tumor immune response of organisms by regulating the immune cell composition and the T cell function in the tumor microenvironment, so that the treatment effect of the immune checkpoint inhibitor is improved, and a new theoretical basis and application prospect are provided for GABA as an auxiliary strategy for improving the curative effect of tumor immunotherapy.

Inventors

ZHANG WEI
WANG QUANLIN
JING XIANG
CHENG LI
ZHOU HONGHAO

Assignees

中南大学湘雅医院

Dates

Publication Date: 20260512
Application Date: 20260326

Claims (10)

1. Use of gamma-aminobutyric acid in any one of the following: (1) Preparing an antitumor immune effect enhancer; (2) Preparing a potentiator of an immune checkpoint inhibitor in tumor treatment; (3) The combination of immune checkpoint inhibitors produces a medicament for the treatment of tumors.
2. The use of claim 1, wherein the immune checkpoint inhibitor comprises a PD-L1 antibody.
3. The use of claim 1, wherein the tumor is a solid tumor.
4. The use of claim 3, wherein the solid tumor comprises colorectal cancer.
5. A medicament for treating a tumor, the medicament comprising gamma-aminobutyric acid and an immune checkpoint inhibitor.
6. The medicament of claim 5, wherein the immune checkpoint inhibitor comprises a PD-L1 antibody.
7. The medicament of claim 5, wherein the tumor is a solid tumor.
8. The medicament of claim 7, wherein the solid tumor comprises colorectal cancer.
9. The medicament of claim 5, further comprising a pharmaceutically acceptable excipient.
10. The medicament of claim 9, wherein the adjuvant comprises at least one of diluents, fillers, excipients, binders, wetting agents, disintegrating agents, absorption enhancers, surfactants, adsorption carriers, lubricants, and flavoring agents.

Description

Application of gamma-aminobutyric acid in preparation of synergist of immune checkpoint inhibitor Technical Field The invention relates to the technical field of tumor treatment, in particular to application of gamma-aminobutyric acid in preparing a synergist of an immune checkpoint inhibitor. Background In recent years, immune checkpoint inhibitors (immune checkpoint inhibitors, ICIs) have become an important breakthrough in the field of tumor therapy. The medicine can restore the anti-tumor immune function of T cells of organisms by blocking immune inhibition signal paths such as programmed death receptor 1 (PD-1) and ligand PD-L1 thereof, thereby playing a role in inhibiting tumor growth. At present, PD-1/PD-L1 related immune checkpoint inhibitors have been clinically applied to various tumor types, and have achieved remarkable curative effects in the treatment of various malignant tumors such as melanoma, non-small cell lung cancer, renal cancer and the like. However, in clinical practice, only a fraction of patients are able to obtain sustained clinical benefit from immune checkpoint inhibitor treatment, and a significant proportion of patients still have limited response to such treatment or develop primary tolerance. In addition, in some patients, even if the initial treatment achieves a certain effect, secondary drug resistance may develop during the subsequent treatment. Therefore, how to further improve the therapeutic effect of the immune checkpoint inhibitor and expand the applicable population of the immune checkpoint inhibitor in different tumor types is an important technical problem to be solved in the current tumor immunotherapy field. The above problems are particularly pronounced in solid tumors such as colorectal cancer. Although immune checkpoint inhibitors show a better therapeutic effect in a few colorectal cancer patients with microsatellite highly unstable (microsatellite instability-high, MSI-H) or mismatch repair defects (dMMR), their therapeutic response rate is still low in the vast majority of microsatellite stabilized (microsatellite stable, MSS) patients. This phenomenon suggests that a number of factors in the tumor immune microenvironment may have a significant impact on the sensitivity of immune checkpoint therapy. Therefore, development of an adjuvant therapy strategy capable of improving tumor immune microenvironment and improving the curative effect of immune checkpoint inhibitors has become one of the important directions of current tumor immunotherapy research. Recent studies have gradually shown that metabolic regulation factors in the tumor microenvironment play an important role in regulating the immune response of the body. Various small molecule metabolites in tumor tissues not only participate in the cellular energy metabolism and signal transduction process, but also can change the anti-tumor immune response of the organism by influencing the activation state, the cellular infiltration degree and the cytotoxicity function of immune cells. For example, some metabolites can modulate the functional status of immune cells such as T cells, macrophages, dendritic cells, etc., thereby affecting the composition of the tumor immune microenvironment. Therefore, the small molecular active substances which can regulate the tumor immune microenvironment and help to improve the curative effect of the immune checkpoint inhibitor are searched, and the method has important research significance and potential application value. Gamma-aminobutyric acid (gamma-aminobutyric acid, GABA) is a naturally occurring small molecule compound and is widely distributed in various organisms such as animals, plants and microorganisms. GABA was first found to play a key role in nerve signaling, neuromodulation, and maintenance of nervous system homeostasis as an important inhibitory neurotransmitter in the central nervous system. Recent studies have found that GABA has important physiological functions not only in the nervous system but also may be involved in the immune regulation process and exert an influence on the functions of various immune cells. In addition, GABA is also widely found in a variety of foods and dietary sources, such as fermented foods, grains, beans, and partially functional foods, and has been developed as a dietary supplement or a functional food ingredient, having a certain application foundation in the fields of foods and health products. Although studies have shown that GABA may be involved in immune regulation, the mechanism of action of GABA in tumor immune regulation is still not completely understood, and particularly, whether it can affect the anti-tumor efficacy of immune checkpoint inhibitors by modulating tumor immune microenvironment has been still limited. Therefore, the potential role of GABA in tumor immunotherapy is explored, the application value of GABA in improving the curative effect of immune checkpoint inhibitors is evaluated, and the GABA has impo