CN-121971435-A - Application of 3-indole-lactic acid in preparation of product for improving NK cell antitumor capability

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of 3-indole-lactic acid in preparation of a product for improving NK cell antitumor capability. The invention makes clear the relation between 3-indole-lactic acid and NK cell effector functions of HCC patients, reveals that ILA can promote the formation of NK cell immune synapses, enhance target cell lysis capacity of the ILA, inhibit liver cancer progression, and has new application value in correcting NK cell function exhaustion of HCC patients or in correcting the NK cell function exhaustion of HCC patients, and research results are expected to provide new strategies and new ideas for anti-liver cancer treatment.

Inventors

• HAN QIUJU
• WANG JUN
• DOU QIANQIAN
• YU ZHE
• LI RUIXIU
• LI HAOHAO
• ZHAO HUAJUN
• ZHANG JIAN

Assignees

• 山东大学

Dates

Publication Date

20260505

Application Date

20260408

Claims (10)

1. The application of 3-indole-lactic acid in preparing a product for improving the anti-tumor capability of NK cells is characterized in that the tumor is liver cancer.
2. 2. The use according to claim 1, wherein the product has any one of the following functions: (1) The binding rate of NK cells and liver cancer cells is improved; (2) Increasing NKG2D total protein and extracellular protein expression of NK cells; (3) Enhancing F-actin density; (4) Increase production of NK cell effector molecules; (5) Inhibiting proliferation of liver cancer cells; (6) Promoting apoptosis of liver cancer cells; (7) Enhancing the sensitivity of liver cancer cells to NK cell killing; (8) Promote effector functions of CD8 + T cells.
3. 3. The use of claim 2, wherein the NK cell effector molecules include TNF- α, IFN- γ, CD107a, perforin and granzyme B.
4. 4. The use according to claim 1, wherein the product is a medicament.
5. 5. The use of claim 4, wherein the medicament further comprises a pharmaceutically acceptable adjuvant.
6. 6. The use according to claim 5, wherein the auxiliary material is selected from one or more of a osmoprotectant, a non-osmoprotectant, a crystal solution and a pH adjuster.
7. 7. The use according to claim 6, wherein the osmoprotectant is selected from DMSO and the non-osmoprotectant is selected from one or more of adenosine, low molecular dextran, lactobionic acid, HEPES, reduced L-glutathione, glucose, sucrose, mannitol, compound amino acids, plant-derived recombinant human serum albumin.
8. 8. The use according to claim 6, wherein the crystal solution and the pH adjuster are selected from one or more of sodium hydroxide, sodium gluconate, sodium acetate, potassium hydroxide, sodium chloride, calcium chloride, magnesium chloride, potassium bicarbonate, potassium phosphate, calcium chloride, magnesium chloride.
9. 9. The use of claim 4, wherein the medicament further comprises one or more of hydroxyethyl starch, SUL-109, malate buffer, acetate buffer.
10. 10. A method for improving the anti-tumor capability of NK cells for in-vitro non-therapeutic purposes is characterized by comprising the step of adding 3-indole-lactic acid into an NK cell culture system, wherein the tumor is liver cancer.

Description

Application of 3-indole-lactic acid in preparation of product for improving NK cell antitumor capability Technical Field The invention belongs to the technical field of medicines, and particularly relates to application of 3-indole-lactic acid in preparation of a product for improving NK cell antitumor capability. Background Hepatocellular carcinoma (Hepatocellular carcinoma, HCC) is a solid tumor with a very high degree of malignancy, with a very strong invasive and metastatic capacity. The total survival rate of HCC patients in 5 years is less than 5%, and drug resistance is easy to generate for chemotherapy. In recent years, the PD-1/PD-L1 immunotherapy based on T cells has a certain curative effect in partial liver cancer patients, but has the problems of low response rate, easy drug resistance and the like, and severely restricts the clinical application of the therapy. Natural killer cells (Natural KILLER CELL, NK) are an important component of the innate immune system, accounting for up to 30% or more of liver lymphocytes, and play an indispensable key role in antiviral and antitumor responses. However, a large number of study data showed that persistent antigen stimulation in tumor microenvironment and immunosuppressive microenvironment resulted in a significant reduction in the number of NK cells infiltrating liver cancer tissue. Furthermore, NK cell effector function of liver cancer patients is severely impaired, and is particularly manifested by reduced immune synapse formation ability and reduced effector molecule production. Therefore, the novel therapeutic strategy taking the enhancement of the anti-tumor capability of NK cells as the core is explored, and the method has important clinical value and scientific significance. Disclosure of Invention In view of the above-mentioned shortcomings of the prior art, the present invention aims to provide the application of 3-indole-lactic acid in the preparation of products for improving the anti-tumor ability of NK cells. In order to achieve the above purpose, the present invention adopts the following technical scheme: in a first aspect of the invention, there is provided the use of 3-indole-lactic acid in the preparation of a product for increasing the anti-tumour ability of NK cells, said tumour being liver cancer. 3-Indole-lactic acid (Indole-3-LACTIC ACID, ILA), also known as 3-indole-acetic acid, DL-indole-3-lactic acid, 3-indole acetic acid, indole-3-lactic acid, 2-hydroxy-3- (1H-indol-3-yl) propionic acid, is a tryptophan (Trp) catabolite with anti-inflammatory and potentially antiviral activity. 3-indole-lactic acid has CAS number 1821-52-9, molecular formula C 11H11NO3, and structural formula。 The invention firstly defines the relation between 3-indole-lactic acid and NK cell effector functions of HCC patients, reveals that ILA can promote the formation of NK cell immune synapses, enhance target cell lysis capacity, inhibit liver cancer progression and has important application value in correcting NK cell function exhaustion of HCC patients. Further, the product has any one of the following functions: The method comprises the steps of (1) improving the binding rate of NK cells and liver cancer cells, (2) improving the expression of NKG2D total protein and extracellular protein of the NK cells, (3) enhancing the density of F-actin, (4) increasing the production of NK cell effector molecules, (5) inhibiting proliferation of the liver cancer cells, (6) promoting apoptosis of the liver cancer cells, (7) enhancing the sensitivity of the liver cancer cells to NK cell killing, and (8) promoting the effector function of CD8 + T cells. Further, the NK cell effector molecules include TNF- α, IFN- γ, CD107a, perforin and granzyme B. Further, the product is a medicament. Further, the medicament also comprises pharmaceutically acceptable auxiliary materials. Further, the auxiliary material is selected from one or more of a permeability protective agent, a non-permeability protective agent, a crystal solution and a pH regulator. Further, the permeability protective agent is selected from DMSO, the non-permeability protective agent is selected from one or more of adenosine, low molecular dextran, lactobionic acid, HEPES, reduced L-glutathione, glucose, sucrose, mannitol, compound amino acid and plant source recombinant human serum albumin, and the crystal solution and the pH regulator are selected from one or more of sodium hydroxide, sodium gluconate, sodium acetate, potassium hydroxide, sodium chloride, calcium chloride, magnesium chloride, potassium bicarbonate, potassium phosphate, calcium chloride and magnesium chloride. Further, the medicament also comprises one or more of hydroxyethyl starch, SUL-109, malate buffer and acetate buffer. In a second aspect of the present invention, there is provided a method for increasing the antitumor ability of NK cells for non-therapeutic in vitro purposes, said method comprising adding 3-indole-lactic acid to an N