PD-L1 IgV affinity peptide S10 with antitumor activity

A technology of anti-tumor activity and affinity peptide, which is applied in the direction of anti-tumor drugs, medical preparations containing active ingredients, peptides, etc.

Active Publication Date: 2014-10-08
ZHENGZHOU UNIV
View PDF2 Cites 21 Cited by
  • 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

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • PD-L1 IgV affinity peptide S10 with antitumor activity
  • PD-L1 IgV affinity peptide S10 with antitumor activity
  • PD-L1 IgV affinity peptide S10 with antitumor activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] The anti-tumor activity targeting PD-L1 IgV affinity peptide S10 provided by the present invention specifically binds to the PD-L1 IgV region and is screened by using phage display peptide library technology. Its amino acid sequence is:

[0021] Trp-Ser-His-Gly-Gly-His-Gln-His-Phe-Ile-Arg-Phe, namely W-S-H-G-G-H-Q-H-FI-R-F, the molecular weight is 1507.7.

[0022] Due to the high cost of monoclonal antibody drugs and the inability to produce them on a large scale, we selected the PD-L1 IgV region protein expressed and purified from prokaryotic cells as the target, and screened the protein that can specifically bind to PD-L1 IgV through phage display technology. Peptides to block PD-1 / PD-L1 signaling pathway. For the convenience of those skilled in the art to implement the present invention, its screening process is briefly described as follows:

[0023] The preparation instructions for the media and master solutions used in the screening process are as follows:

[0...

Embodiment 2

[0076] The affinity peptide S10 of the PD-L1 IgV with anti-tumor activity is synthesized by the Fomc solid-phase peptide synthesis method, and the synthesis steps are briefly described as follows:

[0077] The main reagents used in the synthesis process are:

[0078] Heading liquid: acetic anhydride / pyridine solution (1:1, v / v);

[0079] Indene detection reagent: A. Ninhydrin / ethanol solution (5%, w / v)

[0080] B. Phenol / Ethanol (4:1, w / v)

[0081] C. Potassium cyanide / pyridine (2%, v / v)

[0082] Deprotection solution: piperidine / DMF solution (20%, v / v);

[0083] Cleavage reagent: by volume, TFA (82.5%), H 2 O (5%), phenol (5%), thioanisole (5%), ethanedithiol (2.5%).

[0084] The synthetic steps are briefly described as follows:

[0085] (1) Swell the resin, add the first amino acid

[0086] A. Swelling resin: Take 0.3~0.5 g 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 synthesize...

Embodiment 3

[0128] Taking the PD-L1 IgV affinity peptide S10 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:

[0129] (1) Affinity peptide S10 inhibits the growth of transplanted tumors in mice bearing CT26 colon cancer

[0130] Select 20 experimental Balb / c mice, adjust the cell concentration to 5×10 mouse colon cancer (CT26) cells with normal saline (NS) 6 cells / mL, 0.1 mL 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.

[0131] The affinity peptide S10 prepared in Example 2 was dissolved in physiological saline to prepare a polypeptide drug, which was subpackaged and stored at -20°C for future use.

[0132] Nine days after inoculation with mouse-derived colon cancer (CT26) cells, the mice were divi...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention belongs to the technical field of biological pharmacy, and concretely relates to a PD-L1 IgV affinity peptide S10 product with antitumor activity, and preparation and application thereof. The affinity peptide S10 is specifically bond at PD-l1 IgV region, has the amino acid sequence of WSHGGHQHFIRF, and has the molecular weight of 1507.7. The affinity peptide S10 is prepared through a Fomc solid-phase peptide synthesis method, and plays a role as a main active composition for preparing anti-colorectal carcinoma medicines. The provided affinity peptide S10 is obtained by utilizing a phage-display peptide-library screening technology and taking PD-L1 IgV as a target for performing high-flux screening. Experiments of bearing a cancer in a mouse prove that affinity peptide S10 has relatively good antitumor activity, is capable of obviously inhibiting growth of tumor in a mouse, and provides new thinking and theoretical base for research and exploitation of medicines based on PD-L1.

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 an affinity peptide S10 targeting PD-L1 IgV with anti-tumor activity. Products and their preparation and applications. 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 immune memory to ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07K7/08A61K38/10A61P35/00C07K1/06C07K1/04
Inventor 高艳锋刘蓓媛祁元明李国栋周秀曼李雯雯周杨
Owner ZHENGZHOU UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap