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Tumor neoantigen polypeptide and application thereof

A technology of antigens and variants, applied in the direction of fusion peptides, anti-tumor drugs, cancer antigen components, etc.

Pending Publication Date: 2020-12-22
SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, there is still a lack of a sufficient number of tumor neoantigens with satisfactory effects that can be used as effective targets for tumor therapy

Method used

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  • Tumor neoantigen polypeptide and application thereof
  • Tumor neoantigen polypeptide and application thereof
  • Tumor neoantigen polypeptide and application thereof

Examples

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preparation example Construction

[0111] The preparation methods of the above TCR and antibody are known to those skilled in the art, including but not limited to, expressing and purifying from Escherichia coli cells or insect cells.

[0112] The TCR and / or antibody may be provided to the cell surface, such as the TCR to the surface of a T cell. Therefore, the present invention also provides an isolated monoclonal T cell that binds to the polypeptide-MHC complex of the second aspect of the present invention.

[0113] The present invention also provides the use of the polypeptide and its variant, polypeptide-MHC complex, tandem polypeptide, cell, nucleic acid molecule, molecule or T cell, for preparing a drug for preventing or treating cancer.

[0114] The present invention also provides a pharmaceutical composition, which contains a pharmaceutically acceptable carrier and the peptide, polypeptide-MHC complex, tandem polypeptide, cell, molecule or T cell.

[0115] The pharmaceutical composition is suitable for...

Embodiment 1

[0122] Example 1. HLA-A2 and HLA-A11 high affinity KRAS and HPV16 polypeptides.

[0123] First use the established human papillomavirus T cell antigen database (HPVdb) (Zhang, G.L., et al., HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology. Database (Oxford), 2014.2014: p.bau031.) and promiscuous MHC-binding peptide prediction server to predict HPV16- and KRAS-derived peptides with high affinity to HLA-A2 and HLA-A11, respectively. The present invention predicted 15 HPV16-derived polypeptides (Table 1), which showed binding ability to HLA-A02 and HLA-A11.

[0124] Table 1 Peptides derived from HPV16

[0125] gauge sequence SEQ ID No.: HPV16 E6 7-15 (E6 7-15 )

AMFQDPQER 1 HPV16 E6 9-18 (E6 9-18 )

FQDPQERPRK 2 HPV16 E6 18-26 (E6 18-26 )

KLPQLCTEL 3 HPV16 E6 33-41 (E6 33-41 )

IILECVYCK 4 HPV16 E6 52-60 (E6 52-60 )

FAFRDLCIV 5 ...

Embodiment 2

[0131] Example 2. Polypeptide UV exchange analysis and HLA-ⅠELISA detection

[0132]These predicted peptides were custom-synthesized by Elim Biopharmaceuticals and Jill Biochemical Shanghai Company with a purity of >80%. Synthetic polypeptides were resuspended to 10 mM in deionized water and stored at -80°C.

[0133] Prepare 50 μM and 25 μM polypeptides, 0.025 mg / mL HLA-A02:01 monomer and 0.0125 mg / mL HLA-A11:01 monomer by dilution in 1×PBS. Mix 50 μM peptide and 0.025 mg / mL HLA-A02:01 monomer containing UV-sensitive peptide, or 25 μM peptide and 0.0125 mg / mL HLA-A11:01 monomer containing UV-sensitive peptide in equal volumes on ice. The mixture was incubated under 366nm ultraviolet light exposure for 30 minutes, the UV-sensitive peptides on the human MHC class I molecules were destroyed, the peptide binding sites of the human MHC class I molecules were exposed, and the co-incubated target peptides could bind to the human HLA groove , the HLAⅠmolecular monomer that is not bo...

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Abstract

The present invention relates to tumor neoantigen polypeptide and an application thereof. Specifically, the present invention provides a newly discovered tumor neoantigen polypeptide derived from human papilloma virus HPV16 and KRAS oncogenes, a screening method of the tumor neoantigen polypeptide, a compound formed by the polypeptide and an MHC molecule, and uses of the polypeptide and the compound. and meanwhile, the present invention also provides molecules and cells combined with the polypeptide or the compound, and uses of the molecules and the cells.

Description

technical field [0001] The invention belongs to the field of tumor immunotherapy, and in particular relates to tumor neoantigen polypeptides and uses thereof. More specifically, the present invention relates to the newly discovered tumor neoantigen polypeptide derived from human papillomavirus HPV16 and KRAS oncogene, its screening method, complex and its application. At the same time, the present invention also relates to molecules and cells combined with the above-mentioned polypeptides or complexes, and uses of these molecules and cells. Background technique [0002] Malignant tumors have become the main cause of human death. In China, the National Cancer Center estimated that there were about 3.804 million new cases of malignant tumors and 2.296 million deaths in 2014 based on the 2014 tumor registration data collected and reported by the National Cancer Registry Center [1] , pose a huge threat to national health and bring huge costs to society. So far, the clinical t...

Claims

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Application Information

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IPC IPC(8): C07K14/025C07K14/82C07K19/00G01N33/68A61K39/00A61K39/12A61P35/00
CPCC07K14/005C07K14/82C07K19/00G01N33/68A61K39/0011A61K39/12A61P35/00C12N2710/20022C12N2710/20034C07K2319/40G01N2333/025G01N2333/82A61K39/00C07K14/025A61K38/00
Inventor 王锋
Owner SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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