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Group of markers for predicting storm of immune checkpoint of COVID-19, application and kit thereof

An immune checkpoint, coronavirus technology, applied in the field of biomedicine, can solve problems such as failure to predict patient biomarkers, decreased immune response levels, and decreased antiviral ability, achieving the effects of rapid detection, broad application prospects and low cost

Pending Publication Date: 2021-01-22
BEIJING IMMUPEUTICS MEDICINE TECH LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, in severe cases, the virus-specific T cells in the body are exhausted after excessive activation, and the level of immune response decreases, thereby reducing the body's anti-virus ability.
However, there are currently no biomarkers that predict the occurrence of immune checkpoint storms in patients

Method used

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  • Group of markers for predicting storm of immune checkpoint of COVID-19, application and kit thereof
  • Group of markers for predicting storm of immune checkpoint of COVID-19, application and kit thereof
  • Group of markers for predicting storm of immune checkpoint of COVID-19, application and kit thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0032] In a specific embodiment of the present invention, the preparation method of the kit preferably includes the following steps:

[0033] (1) Will be coated with one or two of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 The above capture antibodies were coupled to the encoded microspheres, and the resulting microspheres were coated with BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 Encoded microspheres of one or more than two capture antibodies;

[0034] (2) One or more detection antibodies in BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 Connect biotin to get one of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 respectively labeled with biotin One or more detection antibodies;

[0035] There is no sequence relationship between the steps (1) and (2).

[0036] The present invention combines one or more capture antibodi...

Embodiment 1

[0061] Preparation of liquid chip kits for detection of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 biomarkers.

[0062] 1. Kit Composition

[0063] (1) 13-plex coated microspheres: containing BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 capture antibody-encoded microspheres;

[0064] (2) 13-plex biotin-labeled detection antibodies: BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 detection antibodies;

[0065] (3) streptavidin phycoerythrin.

[0066] Among them, the clone numbers of capture antibodies BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152 are 6F7, 110416, LH1, The clone numbers of 7H8L17, C9B7W, J116, MIH1, F38-2E2, 10F3, 18, 4B4, O323, 14D3; BTLA, GITR, HVEM, IDO, PD-L1, CD28, CD80, and CD152 detection antibodies are MIH26, DT5D3, eBioHVEM-122, 2E2.6, 10F.9G2, 37407, MEM-233, WKH 203, the detection antibodies of ...

Embodiment 2

[0088] BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152 Liquid Chip Kits in Predicting COVID-19 Immune Checkpoint Storm Applications.

[0089] 1. Purpose of the experiment

[0090] Demonstrated that baseline concentrations of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152 were significantly more 19 patients were moderately high.

[0091] 2. Subjects

[0092] 1) On the premise of informed consent and meeting the inclusion conditions, select the enrolled cases and record personal basic information. The cohort of COVID-19 patients came from 109 COVID patients in Beijing Ditan Hospital affiliated to Capital Medical University, including 5 asymptomatic patients, 60 mild or moderate patients, and 44 severe or critical patients.

[0093] 2) Plasma was drawn from the patients before treatment when they were admitted to the hospital, and the samples were stored in a -80°C refrigerator.

[0094] 3. Reagent Pr...

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Abstract

The invention provides a group of markers for predicting the storm of an immune checkpoint of COVID-19, application, a kit and a preparation method of the kit, which belong to the technical field of biological medicines. The markers provided by the invention comprise one or more than two of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27 and CD152. When the biomarker or the kit prepared from the biomarker provided by the invention is used for predicting the storm of the immune checkpoint of the COVID-19, the biomarker or the kit has the advantages of rapidness and accuracy in detection, low cost and the like, and has a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a group of markers for predicting the immune checkpoint storm of 2019 coronavirus disease, its application and a preparation method of a kit. Background technique [0002] As the coronavirus disease 2019 (COVID-19) continues to spread around the world, the related epidemic has evolved into a global public health crisis. In addition to dyspnea, hypoxemia, acute respiratory distress, and cytokine release syndrome, progressive lymphopenia (especially T cells) is a prominent clinical feature of severe COVID-19. Recently, several studies have found that T cell loss is associated with increased expression of several inhibitory checkpoint molecules on T cells in severe COVID-19 cases. Inhibitory checkpoint molecules have been shown to be key factors regulating T cell exhaustion in various chronic viral infections and cancer patients. Recent studies have further demonst...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68G01N33/543
CPCG01N33/6893G01N33/54313G01N2800/12G01N2333/70521G01N2333/70578G01N2333/70503G01N2333/70532G01N2800/60G01N2800/52Y02A50/30G01N33/58G01N33/56983G01N33/68
Inventor 沈宁孔雅娴王修芳张恒辉宋瑾
Owner BEIJING IMMUPEUTICS MEDICINE TECH LTD
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