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Immune activation type antibody and application thereof

An immune activation and antibody technology, applied in the direction of antibodies, immunoglobulins, antibody medical components, etc., can solve the problems of normal tissue damage and side effects, and achieve the effects of avoiding damage and side effects, good immune regulation and therapeutic effect

Pending Publication Date: 2021-11-19
SHENZHEN KANGJUZHENG PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide an immune activating antibody and its application, aiming to solve the technical problems of existing immune activators that easily cause damage to normal tissues and side effects when activating the immune system

Method used

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  • Immune activation type antibody and application thereof
  • Immune activation type antibody and application thereof
  • Immune activation type antibody and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0160] The synthetic method of compound 1, comprises the steps:

[0161] Dissolve 2.37 grams of compound Pro-1 and 1.2 grams of bromopropionitrile in 50 mL of acetonitrile, and add 1.5 grams of K 2 CO 3 , and stirred at room temperature for 12 hours. After filtration, 2 mL of iodotrimethylsilane was added, and stirred at room temperature for 10 hours. Add 5 mL of saturated NaHCO 3 Solution, the solvent was distilled off under reduced pressure, separated by silica gel column chromatography (methanol:dichloromethane=1:10 volume ratio), the product solution was collected, concentrated under reduced pressure to remove the dissolved solution, and the solid product was obtained as compound 1.

[0162]

[0163] The synthesis method of compound 2 and compound 3 is basically the same as that of compound 1, except that when compound 2 is synthesized, compound Pro-1 is replaced by compound 9; when compound 2 is synthesized, compound Pro-1 is replaced by compound 10 . Among them, ...

Embodiment 1

[0357] TLR7 Activation Detection of the Compound of Example 1 (HEK-BlueTM Detection)

[0358]Take HEK-Blue TMh TLR7 cells in the logarithmic growth phase (purchased from InvivoGen), discard the growth medium (Gibco, C11995500BT, Invivo Gen, ant-nr), and take an appropriate amount of 37°C PBS (Hyclone, SH30256.01) Wash the cells twice by lightly rinsing, and discard the PBS. Add 2-5mL 37°C PBS, incubate for 1-2min, scrape the cells with a cell scraper and blow gently to disperse them into a single-cell suspension. The cells were counted and the cell concentration was calculated using a hemocytometer, and the cell suspension was adjusted to 2.5×104 / 180 μL per well using HEK-Blue™ Dectetion solution (purchased from Invivo Gen) for cell plating on a 96-well cell culture plate. According to the compound or drug concentration (for example, 0.01 μM, 0.1 μM, 1 μM, 5 μM, 15 μM, 30 μM, 40 μM), HEK-BlueTM hTLR7 cells were stimulated, and three replicate wells were set for each concentra...

Embodiment 2

[0359] Example 2 Detection of the TLR7 agonist release effect of each immune-activating antibody

[0360] Take each immune-activating antibody and add it to HER2-positive SKBR3 (10 5 1) cells in RPMI1640 medium. After mixing and culturing for 12 hours, the supernatants were taken out, and the TLR7 activation effect was tested according to the method in Example 1. The result is as figure 2 and image 3 shown.

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PUM

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Abstract

The invention belongs to the technical field of medicines, and particularly relates to an immune activation type antibody and application thereof. The immune activation type antibody provided by the invention comprises an antibody and an immune activator which are coupled through a coupling chain, and can be used for preparing antitumor drugs, antiviral drugs, immunomodulatory drugs and / or preparations for eliminating target proteins. According to the present invention, the antibody and the immune activator are coupled through the coupling chain, such that a series of the immune activation type antibodies targeting the specific tissue, the focus and the target spot can be formed, the local targeting immune activation effect can be achieved, the negative influence of TLR activation on the normal tissue can be solved, and the good specific immune regulation and treatment effect can be provided.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to an immune activation antibody and its application. Background technique [0002] Toll like receptor (TLR) belongs to the classic animal innate immune system. Mammalian and human TLR receptors have 11 members, such as TLR2, TLR3, TLR4, TLR7, TLR9, etc.; each TLR can be activated by specific ligands to resist the invasion of various microorganisms such as bacteria and viruses, and anti-tumor . Among them, TLR7 can be activated by artificially synthesized small molecule immune activators. Although the activation intensity of TLR7 is positively correlated with the ability of immune cells (such as dendritic cells, macrophages, T cells, B cells and NK cells, etc.) to kill tumor cells, non-specific killing also tends to cause immune storms to normal tissues damage side effects. [0003] Therefore, how to reduce or avoid the side effects of immune stimulators on normal ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K47/65A61P31/12A61P35/00A61P37/02A61P43/00C07K16/28
CPCA61K39/3955C07K16/2863C07K16/2827C07K16/2818A61K47/65A61P35/00A61P31/12A61P37/02A61P43/00
Inventor 靳广毅王竹林
Owner SHENZHEN KANGJUZHENG PHARMA TECH