Five hinge regions and their chimeric antigen receptors and immune cells

A technology of chimeric antigen receptors and immune cells, which is applied in the field of biomedicine, can solve the problems of blank hinge region and no curative effect of CAR-T cells, etc., to enhance sensitivity, enhance antigen-specific immune response, and improve therapeutic efficacy Effect

Active Publication Date: 2020-08-07
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, so far, there has been no report of a significant improvement in the efficacy of CAR-T cells
Although the hinge region is an important component of the CAR structure, it is traditionally believed that it only plays a connecting role, so research on whether the hinge region is involved in cell function is basically blank at home and abroad.

Method used

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  • Five hinge regions and their chimeric antigen receptors and immune cells
  • Five hinge regions and their chimeric antigen receptors and immune cells
  • Five hinge regions and their chimeric antigen receptors and immune cells

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Embodiment 1

[0064] 1. Entrust Shanghai Sangong Co., Ltd. to synthesize the corresponding target gene according to the nucleic acid sequence, where the target gene includes 4-1BB V (1-2-3-4-5), 4-1BB V (2-3-4-5) , 4-1BB V(3-4-5), 4-1BB V(4-5), 4-1BB V(5), No-H, CD8a-H, CD28-H and IgG4-H, where CD8a- The structural formula of H is intended as Figure 7 As shown, the nucleotide sequence of CD8a-H is shown in SEQ ID NO.18, and the amino acid sequence encoded by CD8a-H is shown in SEQ ID NO.19; the structural formula of CD28-H is intended to be as shown in Figure 8 As shown, the nucleotide sequence of CD28-H is shown in SEQ ID NO.20, the amino acid sequence encoded by CD28-H is shown in SEQ ID NO.21; the structural schematic diagram of IgG4-H is shown in Figure 9 As shown, the nucleotide sequence of IgG4-H is shown in SEQ ID NO.22, and the amino acid sequence encoded by IgG4-H is shown in SEQ ID NO.23. The target gene was connected to the vector pGEM4Z / GFP / A64 by means of gene cloning. We ...

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Abstract

The invention provides five kinds of hinge regions and their chimeric antigen receptors and immune cells, which belong to the technical field of biomedicine, and the five kinds of hinge regions are respectively hinge region V-5, hinge region V-4-5, hinge region V ‑3‑4‑5, hinge area V‑2‑3‑4‑5 and hinge area V‑1‑2‑3‑4‑5. Using the CAR structure of the hinge region of the present invention, compared with the CAR structure using the traditional hinge region, can significantly improve the antigen-specific immune response of CAR-T cells, enhance the sensitivity of CAR-T cells, and resist exhaustion, thereby enhancing CAR ‑Therapeutic effect of T cells, enhance the curative effect of anti-tumor therapy. At the same time, the CAR containing the hinge region of the present invention is suitable for transfection of immune cells such as T cells and NK cells, and can be widely used in tumor treatment.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to five hinge regions and their chimeric antigen receptors and immune cells. Background technique [0002] The chimeric antigen receptor (Chimeric Antigen Receptor, CAR) preparation technology is a method of using genetic engineering to combine non-MHC-restricted single-chain antibody (scFv) with hinge region (hinge), transmembrane motif (TM ) and T cell activation-related motifs in series, by means of electroporation transfection or virus infection to modify immune cells such as T or NK, endowing them with the ability to recognize and kill tumor cells. T cells modified with CAR have achieved good results in the treatment of hematological malignancies. In 2017, two CAR-T cell products targeting CD19 tumor antigens were approved for marketing in the United States for the treatment of relapsed or refractory children and young adults. Adult acute lymphoblastic leukemia. However, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/705C07K19/00C12N5/10A61K39/00A61P35/00
CPCC07K14/70578C12N5/0636C12N5/0646C07K16/32C07K16/303C07K16/2803A61K39/001112A61K39/0011A61K39/001102A61P35/00C12N2510/00C07K2319/03C07K2317/622C07K14/7051C07K16/00A61K2039/5156C07K2317/73A61K39/001106C07K2317/53
Inventor 储以微王月弟骆菲菲高一源
Owner FUDAN UNIV
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