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Prophylactic or therapeutic drug for benign tumor

A benign tumor and pharmaceutical technology, applied in the field of the composition for preventing or treating familial adenomatous polyposis, the drug for preventing or treating benign tumors, and can solve the problems of weak effect

Pending Publication Date: 2021-09-14
INT INST OF CANCER IMMUNOLOGY INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Aspirin is known to be effective in preventing the development and / or inhibiting the progression of adenomas and adenocarcinomas in familial adenomatous polyposis, but its effect is weak and there is a risk of gastrointestinal bleeding as a side effect of aspirin

Method used

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  • Prophylactic or therapeutic drug for benign tumor
  • Prophylactic or therapeutic drug for benign tumor
  • Prophylactic or therapeutic drug for benign tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0663] (Example 1: Expression of WT1 protein in adenoma of familial adenomatous polyposis)

[0664] This example shows that WT1 protein is expressed in adenomas of human patients with familial adenomatous polyposis.

[0665] (experimental method)

[0666] The small and large intestines of a human patient with familial adenomatous polyposis were formalin-fixed and paraffin-embedded, and paraffin blocks were sectioned to a thickness of 3 μm. To reduce endogenous peroxidase reactions, paraffin sections were washed with 3% HO 2 o 2Solution processed, then deparaffinized in xylene, and after stepwise rehydration with ethanol, for antigen retrieval, in 10 mM Tris EDTA buffer (10 mM Tris, 1 mM EDTA, pH 9.0) in a 70°C oil bath Heat for 25 minutes and heat in an oil bath at 110° C. for 25 minutes and cool at room temperature for 3 hours. The treated sections were reacted overnight at 4°C with anti-WT1 6FH2 mouse monoclonal antibody (Dako Cytomation, Inc., Carpinteria, CA) diluted 1...

Embodiment 2

[0671] (Embodiment 2: in APC Min / + Expression of WT1 protein in mice)

[0672] This example shows that WT1 protein in APC Min / + Expressed in small intestinal adenomas of mice, a model mouse for familial adenomatous polyposis.

[0673] (experimental method)

[0674] 20 weeks old APC Min / + The small and large intestines of (C57BL / 6J) mice were formalin-fixed, and paraffin-embedded, and paraffin blocks were sectioned to a thickness of 3 μm. Paraffin sections were deparaffinized with xylene and, after stepwise rehydration with ethanol, microwaved for 15 min in 10 mM citrate buffer (10 mM sodium citrate, 0.05% Tween 20, pH 6.0) for antigen retrieval . The treated sections were reacted overnight at 4°C with anti-WT1 6FH2 mouse monoclonal antibody (Dako Cytomation, Inc., Carpinteria, CA) diluted 100-fold in PBS containing goat serum. Then, the sections were reacted with a biotinylated anti-mouse IgG antibody (Vector Labs., Burlingame, CA) diluted 100-fold in PBS containing goa...

Embodiment 3

[0677] (Example 3: Administering WT1 Peptide Vaccine to Familial Adenomatous Polyposis Model Mice)

[0678] This example shows the administration of WT1 peptide vaccine to APC Min / + Experimental dosing regimen for mice.

[0679] (experimental method)

[0680] The dosing regimen for the WT1 peptide vaccine is shown in Figure 4 . 100 μg of WT1 126-134 Killer peptide and 45 μg of WT1 35-52 The mixture of helper peptide or PBS was emulsified with IFA Montanide ISA51 adjuvant to obtain WT1 peptide vaccine or control vaccine. WT1 peptide vaccine or control vaccine administered intradermally to 4- to 5-week-old APCs Min / + The flank of the mouse. Immunizations were started from the 5th week of life and performed 8 times at a frequency of once a week. Immunized mice were euthanized 10 days after the last immunization for further analysis. Administration of the WT1 peptide vaccine did not cause organ damage, as shown in Table 3 below.

[0681] table 3

[0682]

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Abstract

The present disclosure provides a prophylactic or therapeutic drug for benign tumor. Provided is a prophylactic or therapeutic drug for benign tumor that comprises a WT1 peptide, an analog thereof, or a nucleic acid molecule encoding the same. In a specific embodiment, the present disclosure provides a prophylactic or therapeutic drug for benign tumor that comprises a WT1 peptide, an analog thereof, or a nucleic acid molecule encoding the same. In a preferred embodiment, the prophylactic or therapeutic drug according to the present disclosure for benign tumor (for example, familial adenomatous polyposis) comprises killer type and / or helper type WT1 peptides. In a further preferred embodiment, the aforesaid WT1 peptide is WT1126 killer peptide and / or WT135 helper peptide. In another aspect, provided are WT1 peptide-specific CTLs, a method for inducing WT1-specific helper T cells and a method for inducing dendritic cells presenting a WT1 peptide.

Description

technical field [0001] The present disclosure includes medicaments and methods for preventing or treating benign tumors. In a specific example, the present disclosure relates to compositions for preventing or treating familial adenomatous polyposis. Background technique [0002] A benign tumor is a tumor without pathologically malignant consequences. Benign tumors are generally considered to be distinct from malignant tumors and do not show a tendency to metastasize or invade. Most benign tumors are asymptomatic, but when they are large in diameter, they can show some symptoms by squeezing other tissues or become malignant and need to be treated or prevented. Therefore, few therapeutic and preventive agents exist for benign tumors. [0003] Familial adenomatous polyposis is an inherited disorder with heterozygous deletion of the tumor suppressor gene APC. From about 20 years of age, homozygous deletion of the APC gene occurs in glandular cells with heterozygous deletion ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/04A61K39/39A61K48/00A61P35/00C07K14/82C12N5/0783C12N5/10C12N15/12
CPCA61P35/00C07K14/82C07K14/4703C12N5/0693A61K39/001153A61K2039/82A61K2039/70A61K2039/55566A61K38/08A61K38/10A61K38/1709A01K2217/077A01K2227/105A01K2267/0331A61K35/17C12N5/0639A61K35/15A61K38/04A61K39/39A61K2039/53A61K2039/545C12N2501/415
Inventor 杉山治夫
Owner INT INST OF CANCER IMMUNOLOGY INC
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