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Composite containing anti-PD-1 gene and polycation and its application in treating cancer

A polycation and complex technology, which is applied in the field of Ming Dynasty, can solve problems such as affecting normal distribution, and achieve the effect of realizing immunotherapy and improving transfection effect.

Inactive Publication Date: 2017-02-22
SHANGHAI YUNSHUN BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cationic liposomes have high transfection activity in vivo and in vitro, however, because the positive charge on the surface affects its normal distribution in the body, and at the same time, due to the selection of cationic lipids, immunogenicity and inflammatory reactions have become inevitable in animal experiments One of the shortcoming (Gao, K.&Huang, L.Nonviral methods for siRNA delivery. Molecular pharmaceuticals 6,651-658(2008).)

Method used

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  • Composite containing anti-PD-1 gene and polycation and its application in treating cancer
  • Composite containing anti-PD-1 gene and polycation and its application in treating cancer
  • Composite containing anti-PD-1 gene and polycation and its application in treating cancer

Examples

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preparation example Construction

[0035] The preparation method of the compound containing anti-PD-1 gene and polycation comprises the following steps:

[0036] The complex can be prepared by mixing the aqueous solution of the polycationic polymer and the aqueous solution of the anti-PD-1 gene, and standing at room temperature for 20-60 minutes.

[0037] Application of the complex containing anti-PD-1 gene and polycation in treating tumors.

[0038] The method for treating tumors with a complex containing anti-PD-1 gene and polycations comprises the following steps:

[0039] The complex containing the anti-PD-1 gene and polycation is co-cultured with T cells to prepare self-secreting anti-PD-1 antibody-T cells, and then the self-secreting anti-PD-1 antibody-T cells are injected into the tumor within the patient's body.

Embodiment 1

[0040] Example 1 The preparation of the formation complex of polycationic polymer polyspermine (PSA) and anti-PD-1 plasmid DNA

[0041] The polyspermine prepared by spermine and the linker 2,6-pyridinedicarbaldehyde was made into an aqueous solution with a concentration of 2 μg / μl, and diluted with sterilized water to 20ng / μl, 40ng / μl, 100ng / μl, 200ng / μl, 1000ng / μl and 2000ng / μl solutions. In addition, the anti-PD-1 gene plasmid DNA was formulated into an aqueous solution with a concentration of 20 ng / μl. Add an equal volume of the polyspermine polymer aqueous solution to the plasmid DNA aqueous solution, vortex for 5 minutes, and let stand for 20 minutes to obtain a series of nanocomposite solutions.

Embodiment 2

[0042] Example 2 The particle size and electric charge of the complex formed by polycationic polymer polyspermine (PSA) and anti-PD-1 plasmid DNA bit representation

[0043] A series of complex solutions prepared by the method of Example 1 are put into the test tank of the BIC90plus particle size potential analyzer, and the mass ratios of PSA and plasmid DNA in the complexes of the series of complex solutions are 0.25, 0.5, 2, 5, 10 , 50, set the test temperature to 25°C, the medium to be water, the viscosity to be 0.89cp, the refractive index to be 1.330, and the light scattering angle to be 90°. , the detection wavelength is 659nm, each sample is tested 3 times, each run time is 2min, and the average particle size is recorded. The result is as figure 1As shown, the results show that the particle size of the nanocomposite is below 200 nm. Its dispersion index all meet the requirements.

[0044] A series of complex solutions prepared by the method of Example 1 were put ...

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Abstract

The invention relates to the technical field of cancer treatment by T cell, and particularly relates to a composite containing anti-PD-1 gene and polycation and its application in treating tumor; the composite includes poly-cationic polymer and anti PD-1 gene in the mass ratio of 1-100: 1. The composite is transfected to the T cell externally, and the secretion anti OD-1 antibody-T cell is prepared, and PD-1 antibody can be generated, thus helping to stop the PD-1 signal, effectively helping the exhausted T cell, and promoting the T cell treatment cancer of antitumor immunity response. Compared with the prior art, the secretion anti OD-1 antibody-T cell can effectively treat tumor and realize the tumor immunological therapy; besides, the composite is free from in-vivo toxicity.

Description

technical field [0001] The present invention relates to the technical field of tumor treatment, in particular to a compound containing anti-PD-1 gene and polycation and its application in treating tumors, in particular to a compound containing anti-PD-1 (programmed death-1) gene The nanocomplex formed with polycations is transfected into T cells in vitro to prepare self-secreting anti-PD-1 antibody-T cells, which can produce PD-1 antibodies, thereby helping to block PD-1 signaling, which can effectively help exhausted T cells Cells, a method of treating tumors with T cells that promote anti-tumor immune responses. Background technique [0002] T lymphocytes target and kill tumor cells expressing this specific antigen. Because of its ability to target and kill tumor cells, CTL therapy has become an ideal solution for individualized tumor treatment, and has received more and more attention from immunologists internationally. But T cells are inactivated due to the production ...

Claims

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Application Information

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IPC IPC(8): C12N15/87A61K48/00
CPCA61K48/0041A61K48/005C12N15/87
Inventor 马孟
Owner SHANGHAI YUNSHUN BIOTECH
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