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Use of combination of PPARG activator with SIRP alpha-antibody in preparing drugs for immunotherapy of tumors

An immunotherapeutic drug and activator technology, which is applied in the direction of anti-tumor drugs, antibodies, drug combinations, etc., can solve the problems of unclear and enhanced SIRPα antibody-mediated tumor immunotherapy, achieve the level of inhibiting growth, and increase the effect of tumor immunotherapy , The effect of tumor immunotherapy is remarkable

Active Publication Date: 2020-12-29
JIANGSU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether PPARG activators enhance SIRPα antibody-mediated tumor immunotherapy remains unclear

Method used

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  • Use of combination of PPARG activator with SIRP alpha-antibody in preparing drugs for immunotherapy of tumors
  • Use of combination of PPARG activator with SIRP alpha-antibody in preparing drugs for immunotherapy of tumors
  • Use of combination of PPARG activator with SIRP alpha-antibody in preparing drugs for immunotherapy of tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: PPARG activators reduce CD47 protein levels

[0028] In this example, the effect of the PPARG activator on the protein level of CD47 was verified. The SW620, HCT-116, and MCF-7 cells were routinely cultured in DMEM complete medium containing 10% fetal bovine serum (FBS), and when they reached 80% confluence under a microscope, they were digested with 0.25% trypsin, and the cells were inoculated in a 6-well plate at 37ºC, 5% CO 2 After overnight in the incubator and the density reaches 70%-90% of the well, the cells were treated for 12 hours with dimethyl sulfoxide (DMSO) as the control group and Pioglitazone, Rosiglitazone, and Troglitazone as the test group.

[0029] (1) Cell lysis and Western blot analysis of CD47 protein expression;

[0030] (2) Collect the cells by centrifugation, filter the cells with a 40 μm filter, 2x10 5 Cells were incubated with fluorescently labeled CD47 antibody, incubated at room temperature for 30 minutes, cells were washed s...

Embodiment 2

[0033] Example 2: PPARG activator inhibits CD47 gene expression

[0034] In this example, the effect of PPARG activator Pioglitazone (PIOG) (50 μM) on CD47 gene expression was verified. SW620, HCT-116, and MCF-7 cancer cells were routinely cultured in DMEM complete medium containing 10% fetal bovine serum (FBS), and when they reached 80% confluence under a microscope, they were digested with 0.25% trypsin. Cells were seeded in 6-well plates and placed at 37ºC, 5% CO 2 After overnight in the incubator and the density reached 70%-90% of the well, the cells were treated with DMSO as the control group and PIOG (50 μM) as the experimental group.

[0035] (1) Cells were lysed after 12 hours of treatment, and CD47 gene expression was analyzed by qPCR;

[0036] (2) The cells were transfected with the CD47 reporter gene plasmid, and the cells were lysed 30 hours later, and the transcriptional activity of the CD47 gene was analyzed by dual fluorescent reporters. image 3 It is the ge...

Embodiment 3

[0037] Example 3: PPARG activator combined with SIRPα antibody significantly inhibits tumor growth

[0038] In this example, the effect of PPARG activator Pioglitazone (PIOG) combined with SIRPα antibody on tumor growth was verified. CT-26 cells (2×10 5 ) were inoculated subcutaneously into C57BL / 6 mice, and the inoculated mice were randomly divided into four groups: IgG (control group), SIRPα antibody, PIOG, and SIRPα antibody+PIOG; IgG / SIRPα antibody was subcutaneously injected every three days (200 μg / mouse), orally administered PIOG (20mg / kg / day) every day. Tumor volume was measured every week for a total of 4 weeks, and mice were sacrificed by neck dislocation at the end. Tumor volume calculation formula = 1 / 2 (length × width 2 ). And Western blot was used to analyze the expression level of CD47 protein in tumor tissue lysates, in which Tubulin was an internal control protein.

[0039] Figure 4 It is the effect of PPARG activator combined with SIRPα antibody on tum...

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Abstract

The present invention relates to the field of immunotherapy of tumors and particularly to a use of a combination of a PPARG activator with an SIRP alpha-antibody in preparing drugs for immunotherapy of tumors. The present invention provides the new use of the combination of the PPARG activator with the SIRP alpha-antibody in preparing the drugs for the immunotherapy of the tumors. A large number of experiments prove that the PPARG activator can significantly reduce a level of CD47 protein and inhibit gene and protein expressions of CD47, and can increase an immunotherapy effect of tumors in combination with the SIRP alpha-antibody drug, and the combination can better inhibit growth of the tumors. Compared with a single SIRP alpha-antibody treatment, the combination of the PPARG activator with the SIRP alpha-antibody can remarkably inhibit a growth level of tumors in mice and has obviously higher inhibition than a single use of common antibody drugs. The combination of the PPARG activator with the SIRP alpha-antibody has an obvious effect in immunotherapy of tumors.

Description

technical field [0001] The invention relates to the field of tumor immunotherapy, in particular to the application of a PPARG activator combined with SIRPα antibody in the preparation of tumor immunotherapy drugs. Background technique [0002] Cancer has become the main death disease at present, and cancer treatment mainly uses radiotherapy, chemotherapy, and surgical resection, but these treatments have limitations such as drug resistance and easy recurrence. A large number of studies have shown that the occurrence of cancer is related to the decline of the body's own immune system function, and in recent years, cancer immunotherapy has become more and more effective, and has become the fourth major solution for cancer treatment. Although immunotherapy has a higher efficacy compared with traditional treatment, it still has certain defects, such as antibody drugs approved by the US Food and Drug Administration (FDA) and acting on immune checkpoints (such as PD-1 ) can effec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K39/395A61P35/00B65D25/24B65D25/28B65D25/10B65D25/02B65D55/14B65D81/07B65D81/05B65D85/68
CPCA61K45/06A61K39/39558A61P35/00B65D25/24B65D25/28B65D25/10B65D25/02B65D55/14B65D81/07B65D81/05B65D85/68A61K2300/00
Inventor 侯永忠董晨苟倩史娟娟
Owner JIANGSU UNIV
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