Tumor-targeted CD38-pH low insertion peptide (pHLIP) fusion peptide

A fusion peptide and tumor technology, applied in the field of CD38-pHLIP fusion peptide, can solve the problems of inability to meet tumor oxygen demand, tumor tissue hypoxia, insufficient supply of nutrients, etc.

Pending Publication Date: 2020-01-17
BEIJING ZEQIN BIOMEDICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The growth of tumors requires a large amount of nutrients, but due to the disorder of tumor neovascularization and its own non-functional capillaries, the supply of nutrients is insufficient and cannot meet the oxygen demand of the tumor's high metabolism, resulting in hypoxia in this part of the tumor tissue.

Method used

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  • Tumor-targeted CD38-pH low insertion peptide (pHLIP) fusion peptide
  • Tumor-targeted CD38-pH low insertion peptide (pHLIP) fusion peptide
  • Tumor-targeted CD38-pH low insertion peptide (pHLIP) fusion peptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Example 1 Synthesis of fusion peptide

[0085] The fusion peptide prepared from the functional domain of CD38 and wild-type pHLIP is represented as CD38-WT in the present invention, and the fusion peptide prepared from the functional domain of CD38 and wild-type pHLIP variant 7 is represented as CD38 in the present invention -var7, the fusion peptide prepared from the functional domain of CD38 and wild-type pHLIP variant 3 is represented as CD38-var3 in the present invention. CD38-WT (SEQ ID NO.20), CD38-var7 (SEQ ID NO.21), CD38-var3 (SEQ ID NO.22) (dissolved in DMSO, synthesized by Hangzhou Zhongpei Biochemical Co., Ltd.).

Embodiment 2

[0086] Example 2 Localization of Fusion Peptides on Tumor Cells Cultured in Vitro

[0087] 1. Cell culture

[0088] MBA-MD-231 cells use DMEM medium containing 10% calf serum, 1.6 million units of gentamycin / ml, at 37°C, 5% CO 2 cultured in a cell culture incubator. Cells were passaged at a ratio of 1:1 after confluence.

[0089] 2. Confocal observation positioning

[0090] MBA-MD-231 cells (5x10 5 Cultivate overnight on the coverslip culture dish, discard the culture supernatant, add PBS with pH 6.3 and 7.4 respectively, add the fusion peptide (60 μg / ml) expressed in Example 1, incubate at 37°C for 1 hour, and discard the supernatant for use Wash 3 times with PBS of corresponding pH, add PBS with pH 6.3 and 7.4, add Daretou-PE or IgG-PE (control antibody) (1:400 dilution) and incubate at 37°C for 30 minutes, discard the supernatant Wash 3 times with PBS of corresponding pH, add PBS of pH 7.4, confocal observation. Grouping: (1) pH6.3 untreated group; (2) pH6.3 fusion pe...

Embodiment 3

[0093] Example 3 Evaluation of the Effect of Fusion Peptide Combined with Antibody Drugs in Treating Tumors

[0094] 1. Reagent materials

[0095] 4T1 cells (purchased from ATCC); 6-8-week-old female Balb / c mice (Victoria); Daretou (Johnson & Johnson).

[0096] 2. Steps

[0097] (1) CD38-WT

[0098] 4T1 cells were inoculated in mouse breast, 2x10 6 cells / only, in a volume of 50 μl.

[0099] When the tumor grows to 50mm 3 , start treatment. Divided into the following four groups: CD38-WT / daretou group (10 rats), Johnson & Johnson group (5 rats), CD38-WT group (5 rats), PBS group (10 rats). Administration method: CD38-WT, 1mg / kg, intravenous injection, administered every other day; Daretuyu, 30mg / kg, intraperitoneal injection, twice a week. Tumor volume and mouse body weight were measured every 3 days.

[0100] When the tumor volume of the control group grows to 1000mm 3 , the administration was terminated.

[0101] (2) CD38-var3

[0102] 4T1 cells were inoculated in ...

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Abstract

The invention discloses a tumor-targeted CD38-pH low insertion peptide (pHLIP) fusion peptide. The fusion peptide is formed by connecting a pHLIP and a functional structure domain of CD38. The tumor microenvironment is acidic, under the acidic environment, the pHLIP can be inserted into a tumor cell membrane, by utilizing the properties of the pHLIP, the CD38 connected with the pHLIP is positionedon the surface of the tumor cell membrane in a targeted mode, through the technology, original tumor cells with tumor cell surfaces not expressing the CD38 can also be marked by the CD38, and thus antibody drugs aiming at the CD38 can exert the effects on the original tumor cells not expressing the CD38 as well. Through the research results, the indications of a specific tumor antibody drug are expanded, and clinical application prospects are good.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a tumor-targeting CD38-pHLIP fusion peptide. Background technique [0002] In recent years, with the rapid development of my country's economy, the people's material and cultural level has been continuously improved, and the lifestyle has also undergone tremendous changes. Along with our living environment, changes have also taken place, such as water quality deterioration, air quality decline, and so on. Due to the change of lifestyle and the decline of environmental quality, great changes have taken place in the causes of death in my country. Non-communicable diseases such as malignant tumors, cardiovascular diseases, and chronic diseases have become the main causes of death in my country. The death rate of the country occupies a large proportion and has become a problem that we cannot ignore. [0003] At present, the commonly used treatment methods for malignant tumors include surge...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K47/64A61P35/00
CPCA61K47/64A61P35/00C07K14/195C07K14/4748C07K2319/10
Inventor 魏化伟杨承刚
Owner BEIJING ZEQIN BIOMEDICAL CO LTD
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