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Immunomodulator, vaccine, cell and application thereof

An immunomodulator and vaccine technology, applied in the direction of blood/immune system cells, animal cells, vertebrate cells, etc., can solve the problems of low response rate, response rate rarely exceeds 15%, and unsatisfactory clinical effects , to achieve a strong anti-tumor effect, enhance immunity, enhance the effect of preventing and/or treating a variety of tumors

Active Publication Date: 2019-11-22
启辰生生物科技(珠海)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of DC vaccines alone usually does not lead to the expected improvement of immunotherapeutic effects, and satisfactory clinical results cannot be obtained
Current clinical trials show that the response rate of DC therapeutic vaccines rarely exceeds 15%, and the overall response rate is low

Method used

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  • Immunomodulator, vaccine, cell and application thereof
  • Immunomodulator, vaccine, cell and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] This example is for the preparation of DNA and mRNA encoding antigens and immune checkpoint inhibitors

[0071] 1. Preparation of DNA and mRNA Constructs

[0072] The DNA sequences encoding the human tumor antigen GPC3 used for in vitro sensitization, the DNA sequences used to encode IL-15, IL-15Ra and TGFBR3 mRNA were respectively constructed, and used for subsequent in vitro transcription reactions. Following the coding sequence is a polyadenosine fragment to make the construct. The coding nucleic acid sequence of IL-15 is shown in SEQ ID NO:1, the coding nucleic acid sequence of IL-15Ra is shown in SEQ ID NO:2, and the coding nucleic acid sequence of TGFBR3 is shown in SEQ ID NO:3.

[0073] 2. In vitro transcription

[0074] The corresponding DNA plasmid prepared in step 1 was first linearized with speI endonuclease, and the linearized plasmid was used as a template, and T7 RNA polymerase was used to transcribe in vitro to prepare mRNA. The prepared mRNA was then ...

Embodiment 2

[0076] This example studies the effects of immunomodulators on T cell responses

[0077] 1. Induction culture of DC cells in vitro

[0078] Aseptically extract 50ml of venous blood from a healthy person, separate peripheral blood mononuclear cells with lymphocyte separation medium in an ultra-clean workbench, add the mononuclear cells to the AIM-V medium, and place them in 37°C, 5% CO 2 Incubate in an incubator to allow monocytes to adhere to the wall. After 2h, the non-adherent cells were removed, and the adherent cells were added to iDC medium (GM-CSF with a final concentration of 800U / mL and IL-4 at 500U / mL were added to the AIM-V medium), and placed at 37°C for 5 %CO 2 Cultured in the incubator for 6 days. Transfer half of the cell culture medium to a centrifuge tube, collect the cells by centrifugation at 500g, remove the supernatant, and add an equal volume of fresh mDC medium, the formula of which is as follows: 1600U / mL GM-CSF and 1000U / mL IL-4, TNF-a (5ng / ml), IL-...

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Abstract

The invention discloses an immunomodulator, a vaccine, a cell and an application thereof. The immunomodulators of the present invention comprise (a) IL-15 or a nucleic acid encoding the same capable of binding to its receptor; (b) an IL-15 receptor alpha or a nucleic acid encoding the same; and (c) a polypeptide comprising an extracellular domain of a TGF beta receptor 3 protein or a nucleic acidencoding the same. On one hand, the immunomodulator can be combined with TGF-beta, and the inhibition effect of the TGF-beta on T cell functions and antigen presentation of DC cells is relieved; and on the other hand, IL-15-IL-15Ra can regulate activation and proliferation of T cells and NK cells, also can promote the ability of DC cells to sensitize T cells, induces stronger anti-tumor specific Tcell response, and shows a stronger anti-tumor effect than traditional DC vaccines.

Description

technical field [0001] The present invention relates to pharmaceutical products, in particular to immunomodulators, vaccines, cells and methods for increasing the ratio of TNF-a+ and / or IFN-r+ cells in lymphocyte populations. Background technique [0002] The body's immune response is first captured by antigen-presenting cells (APCs), and after processing and processing, the antigen information is presented to lymphocytes, and then a series of specific immune responses are triggered. Dendritic cells (DC) are currently considered to be the most functional APCs, and their greatest feature is that they can stimulate the proliferation and activation of naive T cells, and are the central link in initiating, regulating and maintaining specific immune responses. In the body's anti-tumor immunity, cellular immunity mediated by T cells plays an important role. [0003] Studies have found that tumor patients have the characteristics of reduced number of DCs and functional defects. Th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/20A61K47/55A61K38/17A61K39/00A61K47/68A61P37/04C12N5/10C12N5/078
CPCA61K38/179A61K38/1793A61K38/2086A61K39/0011A61K47/55A61K47/6811A61P37/04C07K14/5443C07K14/71C07K14/7155C12N5/0634C12N2510/00A61K2300/00
Inventor 蒋俊林鑫其他发明人请求不公开姓名
Owner 启辰生生物科技(珠海)有限公司
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