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Application of host defense peptide or composition thereof in preparation of drugs for treating tumors

A technology of anti-tumor drugs and compositions, applied in the field of biomedicine to achieve obvious anti-tumor effects

Pending Publication Date: 2020-10-30
王天放 +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although there are many methods for treating tumors in the prior art, there is no report on the combination of vaccines, immune checkpoint inhibitors and caerin 1.1 / 1.9 polypeptides for the preparation of anti-tumor drugs

Method used

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  • Application of host defense peptide or composition thereof in preparation of drugs for treating tumors
  • Application of host defense peptide or composition thereof in preparation of drugs for treating tumors
  • Application of host defense peptide or composition thereof in preparation of drugs for treating tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] MTT assay of caerin 1.1 and mutant caerin 1.1 and caerin 1.9 inhibiting tumor cell growth in vitro

[0069] 5×10 3 Place TC-1 cells or B16 cells in 96-well cell culture plates, add P3, caerin 1.1, mutant caerin 1.1 polypeptide or caerin 1.9 polypeptide at a final concentration of 5, 10, and 15 μg / ml respectively, in 10% calf serum PRMI1640 medium at 37 °C, 5% CO 2 Incubate overnight. The growth of TC-1 (left) and B16 cells (right) was detected by MTT method.

[0070] The results showed that the growth inhibitory effect of mutant caerin 1.1 on TC-1 and B16 was better than that of caerin 1.1.

Embodiment 2

[0072] Effect of triple therapy on Arg1-negative tumor-infiltrating macrophages

[0073] Experimental method: C57 / BL6 mice were subcutaneously inoculated with 5×10 5 TC-1 tumor cells. Three days after tumor inoculation, TC-1 tumor-bearing mice were divided into three groups. 3 mice per group. One group is the control group. The mice are immunized with the vaccine, locally injected with caerin polypeptide in the tumor, and injected with equal volume of PBS of PD-1 antibody. 3 days and 9 days after tumor inoculation, 100 μl of vaccine containing 40 μg Ex (10 μg for each polypeptide) / 10 μg MPLA / 300 μg anti-IL-10 receptor antibody vaccine was injected twice subcutaneously. 300 μg PD-1 antibody twice. On days 3-9 after tumor inoculation, 30 μg of Caerin 1.1 and 1.9 (the weight ratio of Caerin 1.1 and 1.9 in the treatment group was 1:1) or 30 μg of control peptide P3 (GTELPSPPSVWFEAEFK-OH) (control group) were locally injected into the tumor for 7 consecutive days. sky. A grou...

Embodiment 3

[0078] Triple therapy reduces the number of tumor-infiltrating B cells

[0079] Experimental method is the same as embodiment 2.

[0080]The B cell population is the major tumor-associated cell population, accounting for 4.84% of the total number of CD45+ cells isolated from untreated TC-1 tumors. In contrast, the proportion of B cells decreased to 1.61% (87 cells) and 0.26% (15 cells) in the P3-treated and caerin 1.1 / 1.9-treated groups, respectively. GO analysis of B cells revealed enriched biological processes including activation (corrected P value = 9.95E-15), differentiation (corrected P value = 8.27E-07) and proliferation (corrected P value = 3.49E- 10) B cells, which regulate B cell receptor signaling (corrected P value = 3.53E-04) ( image 3 A). KEGG enrichment analysis also revealed that the B cell receptor signaling pathway was the second most important pathway after the ribosome (P value = 5.76E-06), while antigen processing and presentation was also enriched (P ...

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Abstract

The invention belongs to the technical field of biological medicines, and relates to a host defense peptide or a composition thereof, the invention also relates to an application of the polypeptide inpreparation of tumor treatment drugs, and concretely relates to an application of a caerin 1.1 mutant, caerin 1.1 / 1.9 polypeptide, an HPV16 E7 polypeptide vaccine and an immune checkpoint inhibitor in preparation of antitumor drugs. The host defense peptide composition provided by the invention is a caerin1.1 / 1.9 polypeptide composition or the caerin 1.1 mutant / caerin 1.9 polypeptide composition,and the structural formula of the host defense peptide composition is shown in the specification. The weight ratio of the caerin1.1 peptide to the caerin1.9 peptide or the weight ratio of the caerin1.1 peptide mutant to the caerin1.9 peptide is 1: (0.1 to 1); according to the caerin 1.1 mutant, the caerin 1.1 / 1.9 polypeptide (or the caerin 1.1 mutant / caerin 1.9) disclosed by the invention, the tumor microenvironment after treatment by a vaccine and a PD-1 inhibitor can be changed, so that the anti-tumor effect is improved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, relates to host defense peptides or their compositions, and also relates to their application in the preparation of drugs for treating tumors, in particular to caerin 1.1 mutants, caerin 1.1 / 1.9 polypeptides and HPV16 E7 polypeptide vaccines, and immune examination The application of combination of point inhibitors in the preparation of antitumor drugs. Background technique [0002] There are many kinds of malignant tumors, with different properties and types, different tissues and organs involved, different stages of the disease, and different responses to various treatments. Therefore, most patients need comprehensive treatment. The so-called comprehensive treatment refers to the comprehensive use of surgery, chemotherapy, radiotherapy, immunotherapy, traditional Chinese medicine treatment, interventional treatment, microwave treatment and other means according to the patient's physical con...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/46A61K38/17A61K45/06A61K39/12A61K39/395A61P35/00
CPCC07K14/463C07K16/2818A61K45/06A61K39/12A61K39/3955A61P35/00C12N2710/20034A61K38/00
Inventor 倪国颖刘晓松王天放
Owner 王天放