Application of ATF3 in preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug

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

Active Publication Date: 2020-04-10
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

Method used

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  • Application of ATF3 in preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug
  • Application of ATF3 in preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug
  • Application of ATF3 in preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug

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

[0094] 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).

[0095] 1.1 Group settings:

[0096] Scramble+vehicle (control group)

[0097] Scramble+DPCPX (Adora1 inhibition group)

[0098] ShAtf3+vehicle (Atf3 knockdown group)

[0099] ShAtf3+DPCPX (joint intervention group)

[0100] 1.2 Experimental process, see Figure 5 A. 6A:

[0101] 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.

[0102] 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 invention provides an application of ATF3 as a target site detection reagent in preparation of a PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug, an application of ATF3 as the target sitedetection reagent combined with a DPCPX inhibitor in the preparation of the PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug, and an application of ADORA1-ATF3 as the target site detection reagent in the preparation of the PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug. The tumor is a solid tumor, preferably melanoma or lung cancer, and further preferably melanoma or non-small celllung 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 immunity. 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 tumor...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K45/06A61K39/395A61P35/00
CPCA61K39/3955A61K45/00A61K45/06A61K2039/505A61P35/00
Inventor 陈翔匡欣薇刘洪粟娟赵爽
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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