Chimeric antigen receptor for pathogen clearance and application thereof

A chimeric antigen receptor, pathogen technology, applied in receptors/cell surface antigens/cell surface determinants, antibodies, hybrid peptides, etc., can solve problems such as inability to treat infectious diseases and pathogen invasion

Active Publication Date: 2020-12-11
PHARCHOICE THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, in the tumor application of CAR-T, cytokine storms often occur due to the activation of CAR signaling. Therefore, the current CAR design is basically unable to be used for the treatment of severe infectious diseases and pathogen invasion.

Method used

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  • Chimeric antigen receptor for pathogen clearance and application thereof
  • Chimeric antigen receptor for pathogen clearance and application thereof
  • Chimeric antigen receptor for pathogen clearance and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1. Preparation and effect of chimeric polypeptides, recombinant cells against coronavirus SARS-CoV-2

[0045] 1. Preparation of chimeric polypeptide and recombinant cells

[0046] Chimeric polypeptides were designed according to the following structures: (a) signal peptide from CD8; (b) extracellular single-chain antibody variable fragment (scFv), which has specific affinity for coronavirus S protein; (c) from CD8 (d) The intracellular signaling domain from MEGF10; meanwhile, construct the intracellular domain FcRγ and CAR containing CD3ζ (first-generation CAR). The specific structural information of the chimeric polypeptide is shown in Table 1:

[0047] Table 1 The chimeric polypeptide structure against SARS-CoV-2

[0048]

[0049]

[0050]

[0051] Using the method of whole gene synthesis to prepare polynucleotides encoding chimeric polypeptides according to the structure of chimeric polypeptides described in Table 1, a Myc tag was added between the...

Embodiment 2

[0125] Example 2. Preparation and Characterization of Chimeric Polypeptides and Recombinant Cells Against Dengue Virus Infection

[0126] 1. Preparation of chimeric polypeptides and recombinant cells

[0127] According to the method described in Example 1, chimeric polypeptides were designed for dengue virus, related genes were synthesized and recombinant cells were prepared. The cells were EOC 13.31 microglial cells. The structural information of the chimeric polypeptides is shown in Table 23.

[0128] Table 23 is aimed at the chimeric polypeptide structure of dengue virus

[0129]

[0130]

[0131] According to the method in Part 2 of Example 1, the binding ability of the recombinant cells to the viral antigen DENV-1DIII was verified, and the results are shown in Table 24:

[0132] Table 24 Viral protein binding

[0133]

[0134] The results showed that the dengue virus chimeric polypeptide and recombinant cells were successfully prepared, and had a high binding a...

Embodiment 3

[0153] Example 3. Preparation and Characterization of Chimeric Polypeptides and Recombinant Cells Anti-Methicillin-resistant Staphylococcus aureus Infection

[0154] 1. Preparation of chimeric polypeptides and recombinant cells

[0155] According to the method described in Example 1 and Example 2, chimeric polypeptides were designed for methicillin-resistant Staphylococcus aureus, related genes were synthesized and recombinant cells were prepared. The cells were selected from the mouse monocytic cell line RAW264.7, and the chimeric polypeptides were See Table 30 for structural information.

[0156] Table 30 is aimed at the chimeric polypeptide structure of methicillin-resistant Staphylococcus aureus

[0157]

[0158]

[0159] Establish the methicillin-resistant Staphylococcus aureus model according to the method of patent literature (CN 111018999 A), briefly described as follows: BALB / c mouse, SPF grade, female, 6-8 weeks old, body weight 18-20g, international standard ...

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Abstract

The invention provides a chimeric antigen receptor (CAR) polypeptide for pathogens. The chimeric antigen receptor polypeptide is provided with: (a) an extracellular domain comprising one or more antigen binding regions having pathogen-related antigen specificity; (b) a transmembrane domain; and (c) one or more copies of an intracellular signal domain of a 'eat-me' signal receptor, which can be specifically bound to a pathogen antigen and activate an endogenous silence type phagocytic clearance signal. Further, the invention also provides polynucleotides encoding the polypeptide, gene vectors,recombinant cells carrying chimeric antigen receptors, and a composition. The chimeric antigen receptor characteristically mediates recombinant cells to perform phagocytic clearance on the pathogens,and does not significantly release cytokines, so that a 'silence' type pathogen clearing mode is actually realized.

Description

technical field [0001] The present invention relates to a novel chimeric antigen receptor (Chimeric Antigen Receptor, CAR) design scheme and application. The CAR chimeric antigen receptor specifically binds pathogen antigens and activates its intracellular "eat-me" signal at the same time , mediate the phagocytosis of recombinant cells to remove pathogens, and in a process, the recombinant cells do not significantly release cytokines. Background technique [0002] The artificial receptor-engineered cell therapy scheme represented by chimeric antigen receptor T cells (CAR-T) has achieved a series of therapeutic breakthroughs, especially in the application of tumor-related diseases. Broadening the application direction of such artificial molecules is a major problem in this field. The structure of a CAR receptor generally consists of an extracellular recognition domain, a transmembrane domain, and an intracellular signaling domain. Among them, the extracellular recognition d...

Claims

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Application Information

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IPC IPC(8): C07K19/00A61K39/44A61P31/00A61P33/00
CPCC07K14/7051C07K16/00A61P31/00A61P33/00A61K2039/505C07K2319/03C07K2319/02Y02A50/30
Inventor 胡适傅文燕赵健
Owner PHARCHOICE THERAPEUTICS INC
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