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Composition for synergistically improving immune response and application

A technology of immune response and composition, applied in the field of immunology and medicine, can solve the problems of unsatisfactory clinical effect, inability to improve the effect of immunotherapy, and response rate rarely exceeding 15%.

Active Publication Date: 2020-02-28
BEIJING TRICISIONBIO THERAPEUTICS INC
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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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  • Composition for synergistically improving immune response and application
  • Composition for synergistically improving immune response and application
  • Composition for synergistically improving immune response and application

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0055] This preparation example is to prepare the DNA and mRNA encoding the antigen and the composition

[0056] 1. Preparation of DNA and mRNA Constructs

[0057] The DNA sequences used to produce the TGF-β regulatory peptide, PD-1 and IL15 / IL15Rα mRNA encoding the present invention were respectively constructed, and used for subsequent in vitro transcription reactions. Following the coding sequence is a polyadenosine segment. The DNA sequence information is shown in Table 1 below.

[0058] In addition, the coding sequence of human tumor antigen GPC3 for in vitro sensitization is constructed. The coding sequence of GPC3 in the present invention consists of the sequence shown in SEQ ID No.6, and the amino acid sequence consists of the sequence shown in SEQ ID No.7. The sequence of GPC3 is available through the Genebank database. In this example, the antigen disclosed in CN107583042A was used.

[0059] Table-1 DNA sequence list

[0060]

[0061]

[0062] 2. In vitro ...

Embodiment 1

[0065] This example is used to study the effect of the composition of the present invention on T cell response.

[0066] 1. Induction culture of DC cells in vitro

[0067] Aseptically extract 50ml of venous blood from patients with hepatocellular carcinoma, separate peripheral blood mononuclear cells with lymphocyte separation medium in an ultra-clean workbench, add mononuclear cells to 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 2Cultured 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 (configuration of fresh medium for mDC: add AIM...

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PUM

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Abstract

The invention discloses a composition for synergistically improving immune response and application. The composition comprises a precursor comprising IL-15 / IL-15Ralpha compound or capable of forming the same, a precursor comprising TGF-beta regulating peptide or capable of forming the same and a precursor comprising programmed death receptor 1 or capable of forming the same. Ingredients of the composition can synergistically act to improve immune response.

Description

technical field [0001] The invention relates to the fields of immunology and medicine, in particular to a composition and application for synergistically improving immune response. Background technique [0002] In the process of the body's immune response, dendritic cells (DC) are the bridge connecting innate immunity and acquired immunity, and are the key cells for the body to recognize and absorb pathogens and tumor antigens. With the study of tumor immunology, especially the in-depth study of DC vaccines loaded with tumor antigens, it has been found that the infusion of DCs sensitized by tumor antigens can stimulate a stronger immune response. [0003] For example, CN 105030825 A discloses an mRNA-DC lung cancer therapeutic vaccine and its enhanced preparation method and CTL cells, including the following steps: obtaining mRNA of lung cancer stem cells, IL-2 and IFN-γ, and combining mRNA, IL-2 and After IFN-γ was transfected into DCs, they were cultured in vitro. The me...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K38/20A61P37/04C12N5/10C12N15/87
CPCA61K38/2086A61K38/1793A61K38/177A61P37/04C12N5/0639C12N15/87C07K14/71C07K14/4748C07K14/70521C07K14/5443C07K14/7155C12N2510/00A61K2300/00
Inventor 孙圣楠吴斐然文高柳
Owner BEIJING TRICISIONBIO THERAPEUTICS INC
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