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Application of adora1 in the preparation of pd-l1/pd-1 monoclonal antibody tumor immunotherapy drugs

A technology of PD-L1 and anti-tumor immunity, which is applied in the field of PD-L1/PD-1 monoclonal antibody tumor immunotherapy and biology, and can solve problems such as unclear mechanism of action

Active Publication Date: 2021-11-23
XIANGYA HOSPITAL CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In innate immunity, ATF3 interacts with NF-κB and pro-inflammatory cytokines IL-6, IL-12b, toll-like receptor-4 (TLR-4) as an immunomodulator in LPS-treated mice, but Its exact mechanism of action in the immune response remains unclear

Method used

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  • Application of adora1 in the preparation of pd-l1/pd-1 monoclonal antibody tumor immunotherapy drugs
  • Application of adora1 in the preparation of pd-l1/pd-1 monoclonal antibody tumor immunotherapy drugs
  • Application of adora1 in the preparation of pd-l1/pd-1 monoclonal antibody tumor immunotherapy drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] 1. In vivo study on the proliferation of adenosine receptor ADORA1 combined with PD-1 monoclonal antibody against transplanted tumor (melanoma) in mice.

[0039] 1.1 Group settings:

[0040] Scramble+IgG2a (control group)

[0041] shAdora1+IgG2a (Adora1 knockdown group)

[0042] Scramble+PD-1mAb (PD-1 mAb treatment group)

[0043] shAdora1+PD-1mAb (joint intervention group)

[0044] 1.2 Experimental process, see figure 1 A:

[0045] About 6 days before the experiment: 6-8 weeks old C57BL / 6 mice were subcutaneously injected with B16F10 melanoma shAdora1 knockdown cell line 5*10 in the right dorsal wing. 5 20 mice each and the same number of Scramble cell lines (control group).

[0046] Day 0 of the experiment: record the body weight and tumor volume of the mice, when the tumor volume grows to about 100mm 3 Beginning at the beginning of time, mice inoculated with shAdora1 knockdown cell line and Scramble cell line were injected intraperitoneally with PD-1mAb 100ug / ...

Embodiment 2

[0062] 1. The in vivo study of the specific inhibitor DPCPX targeting and inhibiting the proliferation of adenosine receptor ADORA1 combined with PD-1 monoclonal antibody transplanted tumors (melanoma, non-small cell lung cancer) in mice.

[0063] 1.1 Group settings:

[0064] Vehicle+IgG2a (control group)

[0065] DPCPX+IgG2a (Adora1 inhibition group)

[0066] Vehicle+PD-1mAb (PD-1 mAb treatment group)

[0067] DPCPX+PD-1mAb (joint intervention group)

[0068] 1.2 Experimental process, see image 3 A. 4A:

[0069] About 6 days before the experiment: 6-8 weeks C57BL / 6 mice were subcutaneously injected with B16F10 melanoma 5*10 in the right dorsal wing 5 Individual or LLC non-small cell lung cancer 1*10 6 wild-type cell lines, 40 mice each.

[0070] Day 0 of the experiment: record the body weight and tumor volume of the mice, when the tumor volume grows to about 100mm 3 At the beginning of time, the inoculated mice were divided into four groups, respectively, DPCPX 1mg / K...

Embodiment 3

[0092] 1. In vivo study of gene knockdown of transcription factor ATF3 combined with adenosine receptor ADORA1 specific inhibitor DPCPX against proliferation of mouse xenograft tumors (melanoma, non-small cell lung cancer).

[0093] 1.1 Group settings:

[0094] Scramble+vehicle (control group)

[0095] Scramble+DPCPX (Adora1 inhibition group)

[0096] ShAtf3+vehicle (Atf3 knockdown group)

[0097] ShAtf3+DPCPX (joint intervention group)

[0098] 1.2 Experimental process, see Figure 5 A. 6A:

[0099] About 6-8 days before the experiment: 6-8 weeks old C57BL / 6 mice were subcutaneously injected with B16F10 melanoma shAtf3 knockdown cell line 5*10 in the right dorsal wing respectively. 5 Individual or LLC non-small cell lung cancer shATF3 knockdown cell line 1*10 6 , and the same number of Scramble cell lines (control group), 20 mice each.

[0100] Day 0 of the experiment: record the body weight and tumor volume of the mice, when the tumor volume grows to about 100mm 3 Be...

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Abstract

The present invention provides the application of ADORA1 in the preparation of PD-L1 / PD-1 monoclonal antibody tumor immunotherapy drugs, specifically the application of ADORA1 as a biomarker before PD-L1 / PD-1 monoclonal antibody tumor immunotherapy drugs, Or the application of ADORA1 as a target site detection reagent in the preparation of PD-L1 / PD-1 monoclonal antibody tumor immunotherapy drugs, and the combination of ADORA1 inhibitors and PD-L1 / PD-1 monoclonal antibody drugs in the preparation of tumor immunotherapy Use in adjuvant medicine. The tumor is a solid tumor, preferably melanoma or lung cancer, more preferably melanoma or non-small cell lung cancer.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the field of PD-L1 / PD-1 monoclonal antibody tumor immunotherapy. Background technique [0002] In recent years, immune checkpoint blockade (Immune checkpoint blockades, ICB)-related therapies have been widely studied by scientists around the world, and have been used for some malignant tumors, such as malignant melanoma (MM) and non-small cell lung cancer (nonsmall cell lung cancer). lung cancer (NSCLC) has brought enormous clinical benefits. Among them, the clinical application of neutralizing antibodies that block the interaction between programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in multiple tumors has brought breakthroughs in tumor immunotherapy. However, with the deepening of the research, the researchers found that it still has obvious shortcomings. Only less than 40% of tumor patients respond to PD-L1 / PD-1 blocking therapy, or there are primary or secondary ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K39/395A61P35/00G01N33/68G01N33/574
CPCA61K39/39558A61K45/06A61P35/00G01N33/57407G01N33/57423G01N33/68A61K2300/00
Inventor 刘洪匡欣薇陈翔
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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