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Application of inhibitor of calcium-activated chloride channels in tumor immunotherapy

A technology of chloride ion channels and immunotherapy, applied in the application field of inhibitors in tumor immunotherapy, can solve the problems of low efficiency of immunotherapy and limited clinical application, etc., achieve rapid clinical implementation and overcome the limitation of clinical application , to overcome the effect of low efficiency

Pending Publication Date: 2021-07-16
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to solve the problem of low effective rate of immunotherapy and limited clinical application of tumor patients

Method used

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  • Application of inhibitor of calcium-activated chloride channels in tumor immunotherapy
  • Application of inhibitor of calcium-activated chloride channels in tumor immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 PD-1 antibody and CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) have a combined therapeutic effect

[0033] 1. Experimental materials:

[0034] (1) Tumor cell lines: mouse-derived intestinal cancer cell line MC38, mouse-derived melanoma cell line B16-OVA, and mouse-derived breast cancer cell line 4T1.

[0035] (2) Experimental mice: C57BL / 6J mice.

[0036] (3) Drug: murine PD-1 antibody, clone number G4C2;

[0037] (4) Drugs: CaCCs inhibitors, T16Ainh-A01 and CaCCinh-A01.

[0038] 2. Experimental steps:

[0039] (1) will 1×10 6 MC38 cell line, 5×10 5 B16-OVA cell line, 2×10 5 Each 4T1 cell line was subcutaneously injected into immunocompetent C57BL / 6J mice to establish a tumor model.

[0040] (2) The tumor-forming models were divided into 6 groups for drug treatment:

[0041] 1) Control group: given IgG control treatment;

[0042] 2) Treatment group 1: given mouse PD-1 antibody treatment;

[0043] 3) Treatment group 2: T16Ainh-A01 treatment;

[0044]...

Embodiment 2

[0053] Example 2 CaCCs inhibitors enhance the infiltration of activated killer T cells in tumor tissue

[0054] 1. Experimental materials:

[0055] (1) Tumor cell line: murine intestinal cancer cell line MC38.

[0056] (2) Experimental mice: C57BL / 6J mice.

[0057] (3) Drug: murine PD-1 antibody, clone number G4C2; T16Ainh-A01.

[0058] (4) Reagents: Granzyme B-PE flow-type antibody, CD45-PC5.5 flow-type antibody, IFN-γ-BV421 flow-type antibody, Zombie UV flow-type antibody, CD8-BV605 flow-type antibody, TCRβ-BV785 flow-type antibody , and other routine reagents for flow cytometry.

[0059] 2. Experimental steps:

[0060] (1) will 1×10 6 A MC38 cell line was subcutaneously injected into C57BL / 6J mice to establish a tumor model.

[0061] (2) The tumor models were divided into 4 groups:

[0062] 1) Control group: given IgG control treatment;

[0063] 2) Treatment group 1: given mouse PD-1 antibody treatment;

[0064] 3) Treatment group 2: T16Ainh-A01 treatment;

[0065...

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Abstract

The invention belongs to the field of biological treatment, and relates to an application of an inhibitor of calcium activated chloride channels (CaCCs) in tumor immunotherapy. Researches show that the inhibitor of the CaCCs can enhance immune infiltration of tumor tissues, and can play a role in synergistically treating tumors with immunotherapy such as a PD-1 antibody and the like. According to the invention, the inhibitor of the CaCCs is combined with the tumor immunotherapy, so that the defects of low effective rate and limited clinical application of the existing immunotherapy can be overcome, and the tumor treatment effect is remarkably improved.

Description

technical field [0001] The present invention belongs to the field of biotherapy. More specifically, it relates to the application of inhibitors of calcium-activated chloride channels (Calciumactivated Chloride Channels, CaCCs) in tumor immunotherapy. When performing immunotherapy on tumor patients, adjuvant CaCCs inhibitors can improve its curative effect, and can overcome the defects of low effective rate and limited clinical application of existing immunotherapy. Background technique [0002] Tumor immunotherapy is an emerging tumor treatment method. Normally, the body's immune system is able to recognize and eliminate alien tumor cells. However, for their own survival and growth, tumor cells adopt different strategies in multiple links of anti-tumor immunity to avoid the killing of the immune system and generate immune tolerance. Tumor immunotherapy is a method of treating tumors by restarting and maintaining the human immune system and restoring the normal anti-tumor ...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K45/00A61K31/513A61K31/381A61K39/395A61P35/00
CPCA61K45/06A61K45/00A61K31/513A61K31/381A61K39/39558A61P35/00A61K2300/00Y02A50/30
Inventor 徐瑞华王峰赵齐王英男
Owner SUN YAT SEN UNIV CANCER CENT
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