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WT1 polypeptide tumor inhibitor

A tumor suppressor, tumor technology, applied in the field of tumor treatment, can solve the problem of complex mechanism of anti-cancer effect

Active Publication Date: 2020-09-11
WINLEIN BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The preparation method of polypeptide antigen is simple, but the mechanism of anti-cancer effect is very complicated. After entering the body, it can be presented to T cells by DC cells to eliminate cancer cells
According to research, the single polypeptide and short peptide antigens (less than 35 amino acids) currently adopted in the world cannot completely cover all patients and produce better curative effect

Method used

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  • WT1 polypeptide tumor inhibitor
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  • WT1 polypeptide tumor inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] According to the results of protein analysis and epitope analysis, figure 1 For WT1 antigenicity analysis, figure 2 For WT1 epitope analysis.

[0021] After codon optimization of WT1 protein, the core region sequence was selected for recombination design and split into 9 polypeptides. Its efficacy is verified by animal experiments.

[0022] The sequences of the 9 polypeptides are as follows:

[0023]

[0024]

Embodiment 2

[0026] (1) Modeling scheme

[0027] According to the experimental objectives, it is proposed to establish four animal models including rectal cancer, colon cancer, liver cancer and breast cancer

[0028] (2) Modeling process

[0029] Cultivate WT1 high expression tumor cell lines;

[0030] Transplant tumor cells into CDX mice;

[0031] CDX mouse model grows to 100mm 3 After that, the grouping is done as follows:

[0032] Negative control group (PBS), original protein W-P001 of the experimental treatment group, recombinant protein W-P001 (342-449) of the experimental treatment group, polypeptides of the experimental treatment group (9 kinds of polypeptides are mixed according to 9 equal molar parts), a total of four groups , 2 mice each.

[0033] 3. Dosing regimen

[0034] Each mouse was administered once every 5 days, 2 mg, and injected in multiple places in the mouse lymph.

[0035] Experimental results:

[0036] Preliminary results of administration of breast cancer ...

Embodiment 3

[0039] To study the antitumor effects of three drugs at different doses in CT26-hWT1 (colon cancer) and 4T1-hWT1 (breast cancer) tumor subcutaneous xenograft mouse animal models.

[0040] experimental design

[0041] This experiment mainly includes two parts: the model experiment in the early stage and the efficacy test in the later stage.

[0042] Experimental group

[0043] Control group, W-P001(342-449)(low dose), W-P001(342-449)(medium dose), W-P001(342-449)(high dose), W-P001(low dose), W-P001 (medium dose), W-P001 (high dose), peptide (low dose), peptide (medium dose) and peptide (high dose) 10 groups, 6 rats in each group, two kinds of cells, 120 rats in total.

[0044] Experimental treatment group of polypeptides (9 kinds of polypeptides were mixed according to 9 equimolar portions).

[0045] Previous model experiments:

[0046] Table 1. Experimental design of mouse subcutaneous tumor model

[0047]

[0048]

[0049] Subcutaneous efficacy test

[0050] See ...

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Abstract

The invention discloses and provides an antigen composed of nine polypeptides from a WT1 protein sequence. According to the antigen, a WT1 target is analyzed through computer software, sequence splitting is carried out on the part, with the best antigenicity, of a protein, and split polypeptides are combined into nine long peptides as antigen sequences. The polypeptide combination disclosed by theinvention has the advantages of better antitumor effect and wider lineage.

Description

technical field [0001] The invention relates to the field of tumor treatment, in particular to a WT1 polypeptide tumor inhibitor. Background technique [0002] The key to active specific immunotherapy of malignant tumors is to select the appropriate antigen target. In 2009, the National Cancer Institute (NCI) analyzed and compared 75 malignant tumor antigens, and finally found that nephroblastoma 1 (nephroblastoma or Wilm's tumor1, WT1) is the best malignant tumor antigen. [0003] The preparation method of polypeptide antigen is simple, but the mechanism of anti-cancer effect is very complicated. After entering the body, it can be presented to T cells by DC cells to eliminate cancer cells. According to research, the single polypeptide and short peptide antigens (less than 35 amino acids) currently used in the world cannot completely cover all patients and produce good curative effect. At present, the indications developed for this target in the world are mainly concentrat...

Claims

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Application Information

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IPC IPC(8): C07K14/47A61K39/00A61P35/00
CPCC07K14/4748A61K39/001153A61P35/00A61K2039/812A61K2039/82
Inventor 李坤鹏
Owner WINLEIN BIOTECH CO LTD
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