Multi-epitope combined peptide used for treating and preventing human papillomavirus infection and related diseases

A multi-epitope and epitope peptide technology, applied in the direction of viral peptides, viruses, hybrid peptides, etc., can solve the problems of unsatisfactory effect, poor effect, short half-life, etc.

Inactive Publication Date: 2018-08-17
HEFEI RUICHENGSHENG BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, although a single ordinary T cell epitope peptide can stimulate an anti-HPV immune response to a certain extent, the effect is not good because the affinity between a single HPV16 / 18E6 and E7 T cell epitope peptide and MHC-I molecules is not high enough, Easily degraded by a variety of peptidases and short half-life, making it unsatisfactory to stimulate T cell responses in vivo

Method used

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  • Multi-epitope combined peptide used for treating and preventing human papillomavirus infection and related diseases
  • Multi-epitope combined peptide used for treating and preventing human papillomavirus infection and related diseases
  • Multi-epitope combined peptide used for treating and preventing human papillomavirus infection and related diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: Multi-epitope combination peptide induces and activates HPV-specific DC-CIK immunity

[0041] Experimental group: the multi-epitope combination peptide fragment HSP70 407-424-AAA-HPV16 E7 11-19 artificially synthesized by Fmoc solid-phase synthesis method. The HSP70407-424-AAA-HPV16 E7 11-19 was dissolved in PBS at a concentration of 1 mg / ml, filtered and used for later use.

[0042] Control group: HPV 16E7 11-19 epitope peptide of HPV16E7 T cells artificially synthesized by Fmoc solid-phase synthesis method. The HPV16 E7 11-19 was dissolved in PBS to a concentration of 1 mg / ml, filtered and used for later use.

[0043] The Ficoll density gradient centrifugation method separates peripheral blood mononuclear cells, the purity is above 90%, the harvest rate can reach 80-90%, and the percentage of living cells is above 95%.

[0044] (1) Preparation of DC-CIK cells

[0045] After the PBMCs were washed twice with 0.9% normal saline, the cell concentration was a...

Embodiment 2

[0075] Embodiment 2 Mouse tumor-bearing model animal test

[0076] The 6-8 week-old, female, C57BL / 6 mice used in the present invention were randomly divided into 3 groups, namely blank group, control group and test group. There were 35 mice in each group (15 mice were used for the prevention model, 15 mice were used for the treatment model, and the other 5 mice were used for the re-challenge test of transplanted tumors), of which 15 mice were used for the prevention model or the treatment model. Of the mice, 5 were tested for tumor morphology, 5 for survival rate testing, and 5 for immunological testing. Specifically, the immune substance injected in the test group was HSP70 407-424-AAA-HPV16E7 11-19 multi-epitope combination peptide vaccine; the immune substance injected in the control group was HPV16E7 11-19 T cell antigen epitope peptide vaccine; the blank group was injected with Aseptic PBS was used as a blank control for the prevention and treatment of HPV16-infected mo...

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Abstract

The invention relates to a multi-epitope combined peptide used for treating and preventing human papillomavirus (HPV) infection and related diseases. The multi-epitope combined peptide consists of a binding domain and a hinge domain of carboxyl-terminated peptide of mycobacterium tuberculosis heat shock protein 70 (HSP70), and antigen epitope peptides of T cells of HPV E6 and E7, and the multi-epitope combined peptide is in linear arrangement through the arrangement mode of HSP stimulated epitope peptide-hinge area-HPV CTL epitope. The multi-epitope combined peptide provided by the invention can be used as a vaccine to induce the immune response mediated by specific T lymphocytes through injection of intradermal, hypodermic, focus or mucosal tissues, and can induce effective antiviral effect in tissues and local tissues for treating and preventing HPV infection and related diseases. The multi-epitope combined peptide provided by the invention has the advantages of low use dose and no need of adding artificial excipients.

Description

technical field [0001] The invention relates to a multi-epitope combined peptide for treating and preventing human papillomavirus (HPV) infection and related diseases caused by it. Specifically, the present invention relates to a multi-epitope combination peptide for cross-inducing human T cell proliferation and HPV-specific T lymphocyte response; a vaccine composition comprising the multi-epitope combination peptide; and the composition in Application in the preparation and treatment of medicines for HPV-related diseases. Background technique [0002] Human papillomavirus (HPV) and related cervical cancer rank second in the incidence of malignant tumors in women, second only to breast cancer. According to studies on the etiology of cervical cancer, 99% of cervical cancer patients have expression of high-risk HPV DNA. On average, more than 350,000 patients die of cervical cancer every year in the world, and the number is on the rise. Globally, there is an average of one n...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K39/12A61P31/20
CPCA61K39/12A61P31/20C07K14/005C07K14/35C07K2319/00C12N2710/20022C12N2710/20034A61K2039/54A61K2039/572A61K2039/585A61K2039/6043A61K2039/627A61K2039/70A61P35/00
Inventor 孙建中
Owner HEFEI RUICHENGSHENG BIOTECH CO LTD
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