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Predictive biomarker PD-L2 targeted polypeptide for tumor immunotherapy and application of predictive biomarker PD-L2 targeted polypeptide

A biomarker and immunotherapy technology, which is applied in the field of preparation of targeted polypeptides related to tumor immunotherapy, can solve the problems of expression level and activity that are difficult to achieve, and achieve the effect of non-immunogenicity, high tolerance, and small molecular weight

Active Publication Date: 2018-01-09
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] So far, noninvasive, reproducible, and highly accurate detection of tumor PD-1 and PD-L1 / PD-L2 expression levels and activities during or after clinical tumor treatment is still difficult to achieve, so there is an urgent need Specific imaging detection technology to guide tumor treatment

Method used

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  • Predictive biomarker PD-L2 targeted polypeptide for tumor immunotherapy and application of predictive biomarker PD-L2 targeted polypeptide
  • Predictive biomarker PD-L2 targeted polypeptide for tumor immunotherapy and application of predictive biomarker PD-L2 targeted polypeptide
  • Predictive biomarker PD-L2 targeted polypeptide for tumor immunotherapy and application of predictive biomarker PD-L2 targeted polypeptide

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experiment example 1

[0053] Experimental example 1 Construction and screening of the PD-L2 targeting polypeptide screening system of the present invention

[0054] 1) Experimental instruments and materials

[0055] N-methylmorpholine (NMM), piperidine, trifluoroacetic acid (TFA), dichloromethane (DCM), ninhydrin, vitamin C, phenol, tetramethyluronium hexafluorophosphate (HBTU), hexahydro Pyridine, triisopropylsilane (TIS), ethanedithiol (EDT), N,N dimethylformamide (DMF), anhydrous ether, resin, methanol, various Fmoc protected amino acids, MB-Streptavidin (chain Mycoavidin magnetic beads), Streptavidin-HRP (streptavidin-labeled horseradish peroxidase), polypeptide synthesis tube, shaker, vacuum water pump, rotary evaporator, the above reagents and materials were obtained from commercial sources.

[0056] 2) Synthesis of PD-L2 "one bead, one object" polypeptide library

[0057] The Fmoc solid-phase peptide synthesis method is used to synthesize the peptide library. The specific method is to coup...

experiment example 2

[0061] Experimental example 2 Detection of affinity between PLP-1 and PLP-7 polypeptides and PD-L2 and HSA proteins by surface plasmon resonance (SPRi) method

[0062]Spot 1 mg / mL of PLP-1 and PLP-7 polypeptides and 1×PBS on the chip, incubate overnight at 4°C under humid conditions, then wash with 10×PBS for 10 minutes, then wash with 1×PBS for 10 minutes, and finally use Wash twice with deionized water, 10min each time, immerse in 1×PBS containing 5% milk, incubate overnight at 4°C, then wash with 10×PBS for 10min, 1×PBS for 10min, and finally wash twice with deionized water , each time for 10min, blow dry with nitrogen, put the chip on the machine (Plexera HT surface plasmon resonance imaging system).

[0063] The mobile phase was sequentially passed through 1×PBS, 2×PBS, 0.78 μg / mL, 1.56 μg / mL, 3.125 μg / mL, 6.25 μg / mL, 12.5 μg / mL and 25 μg / mL of human PD-L2 and the same concentration of human PD-L2 Serum albumin HSA, recorded and analyzed SPRi signal.

[0064] It can b...

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Abstract

The invention relates to a predictive biomarker PD-L2 targeted polypeptide for tumor immunotherapy and an application of the predictive biomarker PD-L2 targeted polypeptide. The general formula of thepolypeptide is: HX1RX2X3X4X5RIRN. The invention also relates to a DNA fragment encoding the polypeptide, an expression vector expressing the polypeptide, a host cell and a bivalent, a multivalent orpharmaceutical composition formed from the polypeptide. The polypeptide can be used for detecting the expression of PD-L2 in tumor cells and immune cells, can be taken as a detection index for predicting the clinical efficacy of anti-PD-L1 / PD-L2-PD-1 therapy and can specifically distinguish PD-L1 and PD-L2 protein with high homology, thereby having great clinical value and significance for optimization of therapeutic schedules and curative effect monitoring of individual patients.

Description

technical field [0001] The invention relates to the fields of medical biological detection technology and medicinal chemistry, in particular to the screening and application of PD-L2 specific targeting polypeptides, and in particular to a preparation method and application of tumor immunotherapy-related targeting polypeptides. Background technique [0002] At present, with the continuous deepening of research on the mechanism of tumor immune escape, inhibitors targeting immune checkpoints have shown good clinical effects in the treatment of various solid tumors, becoming a milestone event in the history of cancer treatment, making people understand Immunotherapy can truly play an important role in the treatment of malignant tumors. Among them, the PD-L1 / PD-L2-PD-1 pathway, as an important cell cycle checkpoint, plays a specific antigen-dependent negative regulatory role. Their combination can inhibit the immune activity of T cells, and in immune tolerance This is also an im...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K19/00A61K47/64A61K47/42A61K49/00A61K45/00A61P35/00G01N33/574G01N33/68
Inventor 王子华胡志远
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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