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Chimeric antigen receptor T cell for tumor stem cells

A chimeric antigen receptor and tumor stem cell technology, applied in the biological field, can solve the problems of immune damage, manslaughter, and potential safety hazards in the clinical application of CAR-T, and achieve the effect of improving safety.

Inactive Publication Date: 2016-04-20
HENAN UNIV HUAIHE HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] 1. Lack of specific antigen: Since a CAR structure only recognizes one antigen, and currently there are few tumor-specific antigens, the application of CAR-T is limited;
[0011] 2. Manslaughter: Due to the lack of tumor-specific antigens, once non-specific antigens are used to prepare antibodies, there is a possibility of manslaughter after CAR-T is imported into the human body, thus causing immune damage
[0012] The above shortcomings lead to a large safety hazard in the clinical application of CAR-T, and its application is also limited

Method used

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  • Chimeric antigen receptor T cell for tumor stem cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] The specific labeled antigens of pancreatic cancer stem cells are CD24+, CD44+ and CD133+. The chimeric antigen receptor T cells for pancreatic cancer stem cells are chimeric with 3 independent antigen receptors, and the 3 antigen receptors are respectively labeled by scFv with different antigens. It is composed of different functional proteins; antigen receptor 1 is composed of ScFv of CD24 antibody and tyrosine activation motif of intracellular immunoreceptor, of course, it can also be composed of ScFv of CD24 antibody and any one selected from CD28 molecule or CD137 molecule or CD134 The intracellular domain of a costimulatory factor is composed; then antigen receptor 2 and antigen receptor 3 are respectively composed of another costimulatory factor or intracellular immune receptor tyrosine activation motif.

[0034] As one of the preferred schemes, antigen receptor 1 is composed of ScFv of CD24 antibody and intracellular immune receptor tyrosine activation motif CD3-ζ; ...

Embodiment 2

[0053] The specific marker antigens of pancreatic cancer stem cells are CD24+, CD44+ and CD133+. The chimeric antigen receptor T cells for pancreatic cancer stem cells are chimeric with 3 independent antigen receptors.

[0054] Antigen receptor 1 is composed of the ScFv of the CD24 antibody and the intracellular domain of the CD28 molecule; the antigen receptor 2 is composed of the ScFv of the CD44 antibody and the intracellular domain of the CD137 molecule; the antigen receptor 3 is composed of the ScFv of the CD133 antibody and the intracellular immune receptor. The body tyrosine activation motif CD3-ζ is composed; its construction method is the same as in Example 1.

Embodiment 3

[0056] The specific marker antigens of pancreatic cancer stem cells are CD24+, CD44+ and CD133+. The chimeric antigen receptor T cells for pancreatic cancer stem cells are chimeric with 3 independent antigen receptors.

[0057] Antigen receptor 1 is composed of ScFv of CD24 antibody and intracellular domain of CD134 molecule; Antigen receptor 2 is composed of ScFv of CD44 antibody and intracellular immune receptor tyrosine activation motif CD3-ζ; Antigen receptor 3 is composed of CD133 The scFv of the antibody and the intracellular domain of the CD28 molecule are composed; the construction method is the same as in Example 1.

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PUM

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Abstract

The invention provides a chimeric antigen receptor T cell for tumor stem cells. Two to three independent antigen receptors are embedded to the T cell. Each chimeric antigen receptor is formed by combining different antigen binding parts of antibodies of tumor stem cell specific markers and different functional protein, and the functional protein is selected from one or combination of two of an intracellular immunoreceptor tyrosine activation motif, a co-stimulatory factor 1 intracellular structural domain and a co-stimulatory factor 2 intracellular structural domain; an extracellular antibody part is connected with intracellular functional protein through a CD 3-zeta transmembrane domain structure. By selecting and combining the different antigen binding parts of the antibodies of the tumor stem cell specific markers (antigen) and different functional protein, the two to three independent chimeric antigen receptors are constructed, the T cell is activated only after all the two to three chimeric antigen receptors are used for recognizing antigens, and accordingly specific cytotoxicity of the tumor stem cells is achieved, and safety of the tumor stem cells are improved.

Description

Technical field [0001] The invention belongs to the field of biotechnology, and specifically relates to a chimeric antigen receptor for tumor stem cells. Background technique [0002] Chimeric Antigen Receptor T-Cell (CAR-T) is a newly developed cell therapy technology for tumor treatment. This kind of treatment has high specificity and good effect, and it has received the attention of the medical profession. The principle of CAR-T is to combine the antigen binding part scFv (single-chain variable fragments, scFv) of an antibody that can recognize a certain tumor antigen with immunoreceptor tyrosine-based activation motifs (ITAM, usually The intracellular part of CD3-ζ and FcεRIγ) is coupled to a chimeric protein in vitro, and the patient’s T cells are transfected by gene transduction to express the chimeric antigen receptor (CAR). After the patient's T cells are "recoded", a large number of tumor-specific CAR-T cells are generated. [0003] At present, CAR-T lymphocyte technolo...

Claims

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Application Information

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IPC IPC(8): C12N5/0783C07K14/725
CPCC12N5/0636C07K14/705C07K14/7051C07K2319/00
Inventor 朱一帆曹艳萍
Owner HENAN UNIV HUAIHE HOSPITAL