Targeted PD-L1IGV affinity peptide D2 with antitumor activity

An anti-tumor activity and targeting technology, applied in anti-tumor drugs, medical preparations containing active ingredients, peptides, etc.

Active Publication Date: 2016-03-30
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the use of PD-L1 blockers as tumor immunotherapy drugs or adjuvants has good application prospects and safety, but in the prior art, there is still a lack of better PD-L1 blocker products

Method used

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  • Targeted PD-L1IGV affinity peptide D2 with antitumor activity
  • Targeted PD-L1IGV affinity peptide D2 with antitumor activity
  • Targeted PD-L1IGV affinity peptide D2 with antitumor activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] The D-configuration affinity peptide D2 of PD-L1IgV with anti-tumor activity provided by the present invention, which specifically binds to the PD-L1IgV region, is screened by mirror-image phage display peptide library technology, and its amino acid sequence is:

[0025] Lys-His-Ala-His-His-Thr-His-Asn-Leu-Arg-Leu-Pro, namely K-H-A-H-H-T-H-N-L-R-L-P, with a molecular weight of 1459.8.

[0026] Since the peptides obtained by conventional phage display peptide library screening are composed of natural amino acid residues, they are easily degraded by enzymes and have a short half-life in vivo. Therefore, we selected the PD-L1IgV domain protein artificially synthesized from D-configuration amino acids as the target, and screened D-configuration antagonistic peptides through mirror phage display technology, thereby greatly improving its ability to resist enzymatic degradation and extending In vivo half-life of action. For the convenience of those skilled in the art to imple...

Embodiment 2

[0059] The D-configuration affinity peptide D2 of the PD-L1IgV with anti-tumor activity is synthesized by the Fomc solid-phase peptide synthesis method, and the synthesis steps are briefly described as follows:

[0060] The main reagents used in the synthesis process are:

[0061] Heading liquid: acetic anhydride / pyridine solution (1:1v / v);

[0062] Indene detection reagent: A. Ninhydrin / ethanol solution (5%w / v), B. Phenol / ethanol (4:1w / v), C. Potassium cyanide / pyridine (2%v / v);

[0063] Deprotection solution: piperidine / DMF solution (20% v / v);

[0064] Cleavage reagent: by volume, TFA (82.5%), H 2 O (5%), phenol (5%), thioanisole (5%), ethanedithiol (2.5%).

[0065] The synthetic steps are briefly described as follows:

[0066] (1) Swell the resin, add the first amino acid

[0067] A. Swelling resin: Take 0.3~0.5g of Rink resin (the C-terminal amino acid of the peptide connected to the resin is an amide) and place it in a cleaned and dried peptide synthesizer, add an ...

Embodiment 3

[0109] Taking the D-configuration affinity peptide D2 of PD-L1IgV with anti-tumor activity prepared in Example 2 as an example, the inventors conducted further in vivo experiments on tumor-bearing mice. The specific experimental process is as follows:

[0110] (1) Affinity peptide D2 inhibits the growth of transplanted tumors in mice bearing CT26 colon cancer

[0111] Select 24 experimental Balb / c mice, adjust the cell concentration to 5×10 mouse colon cancer (CT26) cells with normal saline (NS) 6 cells / mL, 0.1mL cell suspension (containing 5×10 5 cells) were inoculated subcutaneously in the armpit of the right forelimb of each Balb / c mouse, and the growth of the subcutaneous tumor was continuously observed.

[0112] The affinity peptide D2 prepared in Example 2 was dissolved in physiological saline to make a polypeptide drug, which was subpackaged and stored at -20°C for future use. Nine days after inoculation with mouse-derived colon cancer (CT26) cells, the mice were di...

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Abstract

The invention belongs to the technical field of biopharmaceuticals, and specifically relates to a PD-L1-targeted drug with anti-tumor activity. IgV D-configuration affinity peptide D2 product and its preparation and application. The affinity peptide D2 specifically binds to PD-L1? The IgV region has an amino acid sequence of KHAHHTHNLRLP and a molecular weight of 1459.8. The affinity peptide D2 is prepared by the Fomc solid-phase peptide synthesis method, and plays a role as the main active ingredient in the preparation of anti-colon cancer drugs. The affinity peptide D2 provided by the present invention uses D-PD-L1? IgV was obtained by high-throughput screening as the target. Through tumor-bearing experiments in mice, the inventors proved that the affinity peptide D2 has good anti-tumor activity and can significantly inhibit the growth of tumors in mice, thus providing new ideas and ideas for the research and development of drugs based on PD-L1. theoretical basis.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and specifically relates to the screening, preparation and application of a polypeptide product with anti-tumor activity. More specifically, the invention relates to a D-configuration protein targeting PD-L1IgV with anti-tumor activity. And peptide D2 products and their preparation and application. Background technique [0002] In recent years, the situation of tumor prevention and control is very severe. With the improvement of clinical diagnosis, surgical treatment, chemotherapy and radiotherapy, some patients can get early detection, early treatment, and better prognosis. However, finding new treatment methods and drugs has always been a global challenge. Research hotspots. Compared with traditional treatment methods, tumor immunotherapy can activate or induce tumor patients to establish a specific immune response to tumor antigens, eliminate primary tumor cells, and establish imm...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08A61K38/10A61P35/00C07K1/06C07K1/04
Inventor 高艳锋刘蓓媛祁元明李国栋
Owner ZHENGZHOU UNIV
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