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Compositions and uses for synergistic relief of t-cell exhaustion

A composition and cell technology, applied in the field of immunology and medicine, can solve the problems of not being able to stimulate the immune response of tumor patients well, and the response rate is not high enough

Active Publication Date: 2021-09-21
BEIJING TRICISIONBIO THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, various clinical data show that the single use of a certain immune checkpoint inhibitor, such as an antibody targeting PD-1 / PD-L1, is effective in various cancer types, but there is a problem that the response rate is not high enough
It is suggested that only inhibiting a single immune checkpoint can not stimulate the anti-tumor immune response in tumor patients

Method used

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  • Compositions and uses for synergistic relief of t-cell exhaustion
  • Compositions and uses for synergistic relief of t-cell exhaustion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0058] This preparation example is to prepare the DNA and mRNA encoding the antigen and the composition

[0059] 1. Preparation of DNA and mRNA Constructs

[0060] The DNA sequences used to produce the mRNA encoding IL15 / IL15Rα, soluble TGF-β regulatory peptide, and bifunctional fusion protein of 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.

[0061] In addition, the coding sequence of human tumor antigen GPC3 for in vitro sensitization was constructed. The sequence of GPC3 is available through the Genebank database. In this example, the antigen disclosed in CN107583042A was used.

[0062] Table-1 DNA sequence list

[0063] name serial number IL15\IL15Rα SEQ ID No.1 TGF-β regulatory peptide (with Fc fragment) SEQ ID No.2 bifunctional fusion protein SEQ ID No.12 ...

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Abstract

The invention discloses a composition and application for synergistically relieving T cell exhaustion. The composition of the invention comprises an IL-15 / IL-15Rα complex or a precursor capable of forming an IL-15 / IL-15Rα complex, a soluble TGF-β regulatory peptide or a precursor capable of forming a soluble TGF-β regulatory peptide, Bifunctional fusion protein or its precursor. The components of the composition of the present invention can act synergistically to improve the 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 relieving T cell exhaustion. Background technique [0002] Recently, several immune checkpoint inhibitor drugs targeting PD-1 receptor and its ligands PD-L1 and CTLA-4 have been approved for marketing. These immune checkpoint inhibitors have relatively good clinical efficacy in patients with various tumors such as melanoma, renal cancer, colorectal cancer, non-small cell lung cancer and liver cancer. However, multiple current clinical research data show that only using immune checkpoint inhibitors such as PD-1 / PD-L1 antibodies has a low clinical response rate. For example, in patients with liver cancer, only about 15% of patients can obtain clinical benefits. In more recent studies, the antitumor effect of combinations with PD-1 pathway immune checkpoint inhibitors has been evaluated in clinical models. [0003] Multiple ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/62C12N15/24C12N15/12C12N5/10C12N5/0783A61P35/00
CPCA61P35/00C07K14/5443C07K14/70503C07K14/70521C07K14/7155C07K2319/00C07K2319/30C12N5/0636C12N5/0639C12N2501/15C12N2501/2315C12N2501/51C12N2502/99C12N2510/00
Inventor 孙圣楠文高柳吴斐然
Owner BEIJING TRICISIONBIO THERAPEUTICS INC
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