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Application of ADORA1 in preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug

A technology of PD-L1 and anti-tumor immunity, which is applied in the field of biology, PD-L1/PD-1 monoclonal antibody tumor immunotherapy, and 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) 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 preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug
  • Application of ADORA1 in preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug
  • Application of ADORA1 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 of gene knockdown adenosine receptor ADORA1 combined with PD-1 monoclonal antibody against proliferation of transplanted tumors (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 monoclonal antibody treatment group)

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

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

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

[0046] Experiment day 0: Record the mouse body weight and tumor volume, when the tumor volume grows to about 100mm 3 At the beginning of the hour, mice inoculated with shAdora1 knockdown cell line and Scramble cell line were injected with PD-1 mAb 100ug / mouse / 3 days respectively, a...

Embodiment 2

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

[0063] 1.1 Group settings:

[0064] Vehicle+IgG2a (control group)

[0065] DPCPX+IgG2a (Adora1 inhibition group)

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

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

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

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

[0070] Experiment day 0: Record the mouse body weight and tumor volume, when the tumor volume grows to about 100mm 3 At the beginning of the hour, the vaccinated mice were divided into four groups, received DPCPX 1mg / Kg / mouse, intraperitoneal i...

Embodiment 3

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

[0093] 1.1 Group settings:

[0094] Scramble+vehicle (control group)

[0095] Scramble+DPCPX (Adora1 suppression group)

[0096] ShAtf3+vehicle (Atf3 knock-down group)

[0097] ShAtf3+DPCPX (joint intervention group)

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

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

[0100] Experiment day 0: Record the mouse body weight and tumor volume, when the tumor volume grows to about 100mm 3 At the beginning of the hour, mice inoculated with ...

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Abstract

The invention provides an application of ADORA1 in preparation of a PD-L1 / PD-1 monoclonal antibody tumor immunotherapy drug, specifically relates to an application of ADORA1 as a biomarker to PD-L1 / PD-1 monoclonal antibody tumor immunotherapy before medication, or an application of ADORA1 as a target site detection reagent in preparation of the PD-L1 / PD-1 monoclonal antibody tumor immunotherapy drug, and an application of combination of an ADORA1 inhibitor and the PD-L1 / PD-1 monoclonal antibody drug in preparation of a tumor immunotherapy adjuvant drug. The tumor is a solid tumor, preferably melanoma or lung cancer, and further preferably melanoma or non-small cell lung cancer.

Description

Technical field [0001] The present 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 blockades (ICB) related therapies have been extensively studied by scientists around the world, and are used for some malignant tumors, such as malignant melanoma (MM) and nonsmall cell lung cancer (nonsmall cell lung cancer). The treatment of lung cancer (NSCLC) has brought huge clinical benefits. Among them, the clinical application of neutralizing antibodies that block the interaction of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in multiple tumors has brought a breakthrough in tumor immunotherapy. However, with the deepening of research, researchers found that it still has obvious shortcomings. Only less than 40% of tumor patients respond to PD-L1 / PD-1 blockade therapy, or there is a first or second occurrence during the treatmen...

Claims

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Application Information

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Patent Type & Authority Applications(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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