Fusion protein containing chimeric antigen receptor and application of fusion protein

A chimeric antigen receptor and fusion protein technology, applied in the field of biomedicine, can solve the problems of lack of safe and deliberate targets, complex tumor immune microenvironment, poor treatment effect, etc., and achieve enhanced anti-apoptosis and memory expression type, good potential for clinical application, and the effect of changing the immune microenvironment

Active Publication Date: 2021-09-17
SUN YAT SEN UNIV
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Problems solved by technology

Based on the breakthrough of CAR T in the treatment of blood tumors, CAR T therapy has been further extended to the treatment of solid tumors, and has been explored in various solid tumors including breast cancer, liver c

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  • Fusion protein containing chimeric antigen receptor and application of fusion protein
  • Fusion protein containing chimeric antigen receptor and application of fusion protein
  • Fusion protein containing chimeric antigen receptor and application of fusion protein

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[0070] Example

[0071] 1. Construction of Sirf CAR T cells co-expressing SIRPα-Fc fusion protein

[0072] 1.1 Construction of T2-mCAR molecule co-expressing SIRPα-Fc

[0073] Among the numerous CD47 antibodies or receptor-blocking molecules, we selected the drug under investigation, SIRPα-Fc fusion protein (TTI-621). Compared to the 150 kDa antibody molecule, the molecular weight of SIRPα-Fc is only 90kDa , with better penetration and tissue distribution. And the human-derived SIRPα-Fc fusion protein has been confirmed to be able to bind to CD47 molecules on the surface of tumor cells in vitro, thereby enhancing the phagocytic function of macrophages and activating the anti-tumor function of the entire immune system. The mouse CAR gene constructed based on the retroviral vector backbone can be efficiently transduced into mouse T cells. We used the original mouse second-generation CAR molecule T2-m28z ( figure 2 On the basis of A) in A), the mCAR structure co-expressing SI...

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Abstract

The invention relates to the field of biological medicine, in particular to fusion protein containing a chimeric antigen receptor and application of the fusion protein. The fusion protein is prepared from the chimeric antigen receptor, 2A peptide, a first signal peptide, a Sirp alpha structural domain and IgG1 Fc which are sequentially connected in series; and the chimeric antigen receptor comprises an scFv region, a hinge region, a transmembrane domain and an intracellular signal transduction region. The Sirf CAR T cell can relieve tumor load and improve the survival rate of tumor-bearing mice, has no obvious blood toxicity and side effects, and has good clinical application potential. The SIRP alpha-Fc fusion protein can enhance the anti-apoptosis and memory phenotype of CAR T cells and change the immune microenvironment of tumor tissues.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular, to a fusion protein containing a chimeric antigen receptor and its application. Background technique [0002] Malignant tumors have become one of the leading causes of death worldwide. With the continuous development of science and technology, the early diagnosis and treatment of cancer has been able to greatly improve the cure rate of cancer and improve the quality of life of patients. However, most malignant tumors still have problems such as poor prognosis and easy recurrence. Among all tumor treatment methods, immunotherapy has received constant attention and expectation from researchers. The biggest feature of immunotherapy is to use the immune system itself to fight cancer, including antibody therapy, cell therapy and immunomodulatory therapy. Among them, the particularly interesting cell therapy refers to the infusion of cell preparations into the patient, thereby activ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N5/10A61K39/00A61P35/00
CPCC07K14/70596C07K14/7051C07K14/70521C12N5/0636A61K39/001129A61P35/00C07K2319/30C07K2319/02C07K2319/03C07K2319/33C07K2319/00C12N2510/00A61K2039/5156
Inventor 黄朝峰陈焕鹏
Owner SUN YAT SEN UNIV
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