Application of STAT3 inhibitor and STAT5 activator in enhancing lethality of NK (Natural Killer) cell to tumor cell

A technology of NK cells and tumor cells, applied in the field of immunity, can solve the problems that NK cells have no reported lethality to tumor cells, and the use of STAT5 activators has not been reported.

Inactive Publication Date: 2018-08-31
许军
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The use of Flexilarin F and Flexilarin G as STAT3 inhibitors and STAT5 activators has not been reported in the prior art, nor has it been reported that they can improve the lethality of NK cells against tumor cells

Method used

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  • Application of STAT3 inhibitor and STAT5 activator in enhancing lethality of NK (Natural Killer) cell to tumor cell
  • Application of STAT3 inhibitor and STAT5 activator in enhancing lethality of NK (Natural Killer) cell to tumor cell
  • Application of STAT3 inhibitor and STAT5 activator in enhancing lethality of NK (Natural Killer) cell to tumor cell

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Experimental program
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Embodiment 1

[0023] 1. Experimental materials

[0024] RPMI-1640 and fetal bovine serum (FBS) were purchased from GIBCO; NK cell culture medium was purchased from CellGro, Germany.

[0025] Recombinant human interleukin 2 (rhIL-2) was purchased from Shuanglu Pharmaceutical; lymphocyte separation liquid was purchased from NycomedPharma.

[0026] Human gastric cancer cells SGC-7901 and BCG-823 were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences.

[0027] 2. Experimental method

[0028] 1. Mononuclear cell isolation, grouping and NK cell culture

[0029] Peripheral blood from healthy volunteers was collected and subjected to Ficoll density gradient centrifugation to separate peripheral blood mononuclear cells (PBMC). On Day 0, use NK cell culture medium containing 5% autologous plasma and 80 U / ml gentamycin to adjust the PBMC to the initial cell number of 1.0×10 6 / L, divide the cells into the control group and the treatment group, the control group is routinely ...

Embodiment 2

[0052] A STAT3 inhibitor, containing Flexilarin F or Flexilarin G, also contains a pharmaceutically acceptable carrier or excipient, made into a pharmaceutically acceptable dosage form; the pharmaceutically acceptable carrier or excipient includes one or more A solid, semi-solid or liquid excipient, and pharmaceutically acceptable dosage forms include tablets, capsules, granules, injections, pills, syrups, powders, and ointments.

Embodiment 3

[0054] A STAT5 activator, containing Flexilarin F or Flexilarin G, also contains a pharmaceutically acceptable carrier or excipient, made into a pharmaceutically acceptable dosage form; the pharmaceutically acceptable carrier or excipient includes one or more A solid, semi-solid or liquid excipient, and pharmaceutically acceptable dosage forms include tablets, capsules, granules, injections, pills, syrups, powders, and ointments.

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Abstract

The invention discloses application of an STAT3 inhibitor and an STAT5 activator in enhancing lethality of an NK (Natural Killer) cell to a tumor cell. Persons skilled in the art know that by inhibiting STAT3 in a tumor microenvironment, the killing function of immune cells such as NK cells to tumor can be promoted; STAT5 is capable of promoting both growth and development of tumor cells and development and cell toxicity of the NK cells, and by inhibiting STAT5 levels of the NK cells, not only are normal functions of the NK cells damaged, but also growth of tumor can be promoted, so that promotion of expression of STAT5 in the NK cells is beneficial to treatment on tumor. The invention finds that Flexilarin F or Flexilarin G can be used as an STAT3 inhibitor and an STAT5 activator, and byinhibiting expression of STAT3 and activating expression of STAT 5 with the Flexilarin F or Flexilarin G, the lethality of the NK cell to the tumor cell can be improved, and by contrast, diterpene Lobocrassin E has no such function.

Description

technical field [0001] The invention belongs to the field of immunity, and relates to the application of diterpenoids and derivatives thereof in cell immunotherapy, in particular to the application of a STAT3 inhibitor and a STAT5 activator in enhancing the lethality of NK cells to tumor cells. Background technique [0002] In recent years, tumor immunotherapy has made great progress in clinical research and other aspects, but the main research is on T cells in the specific immune system. However, with the in-depth research on natural killer (NK) cells belonging to the innate immune system, their role in tumor immunotherapy has been paid more and more attention. NK cells are an independent subset of lymphocytes that were recently discovered to be the initial members of the innate lymphoid cell family. Different from T cells and B cells, NK cells can kill target cells without specific antigen stimulation, and have the functions of immune clearance and immune surveillance. T...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/365A61P35/00
CPCA61K31/365A61P35/00A61K2300/00
Inventor 徐军
Owner 许军
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