Application of peptide vaccines and microgene vaccines based on CTL epitope peptides of FAPalpha

An epitope peptide, DNA vaccine technology, used in DNA/RNA vaccination, vaccines, medical preparations containing active ingredients, etc.

Active Publication Date: 2018-02-23
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This residue substitution only changes the anchor site, but not the TCR recognition region, i.e. the cross-reactivity of TCR recognition makes the application of this method possible

Method used

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  • Application of peptide vaccines and microgene vaccines based on CTL epitope peptides of FAPalpha
  • Application of peptide vaccines and microgene vaccines based on CTL epitope peptides of FAPalpha
  • Application of peptide vaccines and microgene vaccines based on CTL epitope peptides of FAPalpha

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Embodiment Construction

[0032] 1. Prediction and immunogenicity identification of FAP.291 and FAP.291I9

[0033] 1.1 Prediction of FAP.291 and FAP.291I9

[0034] Based on the human-mouse homology of FAPα and the binding similarity between H2-Kd and HLA-A24, we used the IEDB database to analyze the FAPα human protein HLA-A*2402 restricted epitope and the FAPα mouse protein H2-Kd restriction table. The homologous epitope peptides were predicted, and as a result, three homologous epitope peptides with high affinity to HLA-A*2402 and H2-Kd were obtained, and they were: FAP.291 (YYFSWLTWV, SEQ ID NO :1), FAP.624 (SYGGYVSSL) and FAP.744 (LYTHMTHFL). Then we replaced the C-terminal residues of the three epitope peptides of FAP.291, FAP.624 and FAP.744 with F, L, I, W, and M amino acids that can bind to HLA-A*2402, and To predict their affinity with HLA-A*2402 and H2-Kd, we finally selected three mimetic peptides, FAP.291I9 (SEQ ID NO: 2), FAP.624I9, and FAP.744I9, to effectively improve the affinity for s...

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Abstract

The invention relates to application of peptide vaccines and microgene vaccines based on CTL epitope peptides of FAPalpha, and belongs to the field of tumor peptide vaccines and DNA vaccines with fibroblast activator protein alpha as a target. The invention discloses an FAPalpha derived antitumor epitope peptide FAP.291 and a mimic peptide FAP.291I9 of the FAPalpha derived antitumor epitope peptide FAP.291 and application of microgene DNA vaccines constructed by the FAPalpha derived antitumor epitope peptide FAP.291 and the mimic peptide FAP.291I9 of the FAPalpha derived antitumor epitope peptide FAP.291 in preparation of tumor therapeutic vaccines. Through screening and identification, the epitope FAP.291 and the mimic epitope FAP.291I9 are determined, so that a specific CTL reaction in BALB/c mice can be effectively activated. The invention further relates to application of the vaccines using FAP.291 and FAP.291I9 small peptides in combination with adjuvants and constructing microgene forms of the FAP.291 and FAP.291I9 small peptides in tumor prevention.

Description

technical field [0001] The present invention relates to the fields of tumor CTL epitope peptide vaccines and microgene vaccines, in particular to anti-tumor CTL epitope peptides derived from FAPα, and the present invention also relates to the use of the epitope in the form of peptide vaccines and microgene vaccines in the preparation of anti-tumor vaccines Applications. Background technique [0002] Fibroblast activating protein α (FAPα) is a specific marker on the surface of tumor-associated fibroblasts (CAFs) in the tumor microenvironment, and FAPα is expressed in CAFs of 90% of human epithelial cancer tissues. FAPα is closely related to tumor growth, invasion and metastasis: 1) FAPα dissociates and activates growth factors bound to matrix proteins through enzymatic hydrolysis, which is beneficial to tumor proliferation and angiogenesis, and promotes tumor growth; 2) through collagen Enzyme activity, degrades the extracellular matrix, provides space for angiogenesis to en...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47A61K38/17A61K39/00A61K39/39A61P35/00
CPCA61K39/0011A61K39/39A61K2039/53A61K2039/55505A61K2039/55516A61K2039/55533A61K2039/55561A61K2039/55566C07K14/4748
Inventor 张海红孔维于湘晖张芳芳刘晨露徐平耿飞谢雨郭倩倩陆臻桢
Owner JILIN UNIV
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