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Polypeptide vaccine against tumor-targeted drug resistance sites and design method thereof

A peptide vaccine and tumor targeting technology, applied in the field of peptide vaccines targeting tumor-targeted drug resistance sites and their design, can solve problems such as ambiguity

Active Publication Date: 2019-06-14
HANGZHOU NEOANTIGEN THERAPEUTICS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition to the above two drug resistance pathways, the drug resistance mechanism of the remaining 30% of patients is still unclear

Method used

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  • Polypeptide vaccine against tumor-targeted drug resistance sites and design method thereof
  • Polypeptide vaccine against tumor-targeted drug resistance sites and design method thereof
  • Polypeptide vaccine against tumor-targeted drug resistance sites and design method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0161]Example 2, the construction of the second type of stable cell line at the specific mutation site of Ibrutinib that is resistant to BTK mutations:

[0162] Ibrutinib (ibrutinib) was purchased from Selleck Chemicals, human multiple myeloma cell line RPMI8226 ( CCL-155 TM ) was purchased from ATCC and cultured in RPMI 1640 medium plus 10% fetal bovine serum.

[0163] Purpose of the experiment: In order to verify that the T cells induced by the drug-resistant polypeptides of the present invention have killing activity, it is necessary to construct a set of stable cell lines containing the specific mutation sites of the present invention, capable of expressing and presenting these polypeptides

[0164] a. Construction of mutation site eukaryotic expression plasmid

[0165] The mini-gene capable of expressing all 5 vaccine polypeptides mutated in the present invention is obtained by artificial synthesis, which consists of the following parts: signal peptide part (lysosome-...

Embodiment 3

[0173] Example 3, the construction of the third type of stable transmutation cell line at the specific mutation site of some anti-androgen drugs such as abiraterone for AR drug resistance mutation;

[0174] Prostate cancer cell line PC-3 ( CRL-1435 TM ) was purchased from ATCC and cultured in F-12K medium plus 10% fetal bovine serum.

[0175] Purpose of the experiment: In order to verify that the T cells induced by the drug-resistant polypeptides of the present invention have killing activity, it is necessary to construct a set of stable cell lines containing the specific mutation sites of the present invention, capable of expressing and presenting these polypeptides

[0176] a. Construction of mutation site eukaryotic expression plasmid

[0177] The mini-gene capable of expressing all 4 vaccine polypeptides mutated in the present invention is obtained by artificial synthesis, which consists of the following parts: signal peptide part (lysosome-associated membrane glycopro...

Embodiment 4

[0185] Example 4, the construction of the fourth stable cell line for the specific mutation site of some fennel drugs targeting BRAF drug-resistant mutations;

[0186] Human melanoma cell line A378 was purchased from ATCC and cultured in DMEM medium plus 10% fetal bovine serum.

[0187] Purpose of the experiment: In order to verify that the T cells induced by the drug-resistant polypeptides of the present invention have killing activity, it is necessary to construct a set of stable cell lines containing the specific mutation sites of the present invention, capable of expressing and presenting these polypeptides

[0188] a. Construction of mutation site eukaryotic expression plasmid

[0189]The mini-gene capable of expressing all 7 vaccine polypeptides mutated in the present invention is obtained by artificial synthesis, which consists of the following parts: signal peptide part (lysosome-associated membrane glycoprotein 1, LAMP1), 7 mutated polypeptides and MHC class I traffi...

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Abstract

The invention discloses a polypeptide vaccine against tumor-targeted drug resistance sites and a design method thereof. The design method includes the steps: collecting data of targeted drug resistance mutations; intercepting a drug resistance mutant polypeptide sequence and predicting the affinity and immunogenicity of MHC molecules; obtaining the relationship between targeted drugs and drug resistance sites, and performing drug clustering; and artificially designing a corresponding vaccine polypeptide sequence. The targeted drug combination polypeptide vaccine combination obtained by the method can cover common targeted therapeutic drugs, can effectively reduce the probability of tumor drug resistance, can prolong the effective action time of the targeted drugs, can increase the diseaseresponse rate of the patient, has broad-spectrum, can shorten the time from analysis to treatment of individualized peptide vaccines, and can reduce medical costs.

Description

technical field [0001] The invention relates to the field of tumor vaccines, in particular to a polypeptide vaccine targeting drug resistance sites of tumor targeting drugs and a design method thereof. Background technique [0002] In recent years, the development of tumor targeted therapy has entered a new era with the development of molecular biology technology and the further understanding of pathogenesis from the cellular and molecular levels. The progress in these fields is rapid. So far, many targeted drugs have played an extremely important or even miraculous role in clinical practice. Molecular targeted therapy has become another important means of tumor treatment such as surgery, radiotherapy and chemotherapy, and is playing an increasingly important role in tumor treatment. Due to the high efficiency and low toxicity of targeted therapy, its advantages compared with traditional therapy and chemotherapy are obvious. Targeted therapy has developed rapidly, and some...

Claims

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Application Information

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IPC IPC(8): G16C20/50G16C20/70G16B20/50
CPCG16B15/30G16B20/30G16B20/50G16C20/50G16C20/70Y02A50/30
Inventor 莫凡马治明林志伟韩宁陈荣昌周秀卿陈枢青
Owner HANGZHOU NEOANTIGEN THERAPEUTICS CO LTD
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