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Genetically modified mesenchymal stem cells expressing an immune response-stimulating cytokine to attract and/or activate immune cells

A stem cell and gene modification technology, applied in the field of drugs for the treatment of tumors, can solve the problems of insufficient drug level, insufficient therapeutic benefit, and inability to be administered systemically

Active Publication Date: 2017-05-10
APCETH GMBH & CO KG
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

There are many drugs used to treat cancer that cannot be administered systemically without causing significant unwanted side effects such as fever, elevated levels of liver enzymes, or systemic inflammation, such as a cytokine storm, that may lead to death
One option for avoiding such side effects is to administer significantly reduced doses of such drugs, which, while effective in reducing side effects, often result in insufficient drug levels at the target site and yield insufficient therapeutic benefit

Method used

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  • Genetically modified mesenchymal stem cells expressing an immune response-stimulating cytokine to attract and/or activate immune cells
  • Genetically modified mesenchymal stem cells expressing an immune response-stimulating cytokine to attract and/or activate immune cells
  • Genetically modified mesenchymal stem cells expressing an immune response-stimulating cytokine to attract and/or activate immune cells

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Embodiment Construction

[0148] An important role of the immune system is to identify and eliminate tumors. Transformed cancer cells of a tumor express antigens not found on normal cells. To the immune system, these antigens appear foreign, and their presence causes immune cells to attack transformed tumor cells. Antigens expressed by tumors have several origins. Some antigens are derived from oncogenic viruses such as the human papilloma virus that causes cervical cancer, while others are the organism's own proteins that are present at low levels in normal cell species but reach high levels in tumor cells. One example is an enzyme called tyrosinase that, when expressed at high levels, turns certain skin cells, such as melanocytes, into tumors called melanomas. A third possible source of tumor antigens are proteins often important for regulating cell growth and survival, which often mutate into cancer-inducing molecules called oncogenes.

[0149] The immune system's primary response to tumors is to...

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Abstract

The invention relates to a genetically modified mesenchymal stem cell (MSC) and medical use thereof in the treatment of tumours, said MSC comprising one or more exogenous nucleic acid molecule(s), wherein said exogenous nucleic acid molecule(s) comprise a region encoding one or more immune response-stimulating or immune response-modulating cytokine(s) operably linked to a promoter or promoter / enhancer combination. The invention encompasses the use of said cells in modulating the tumour microenvironment in order to attract immune effector cells and facilitate their activation and / or adoption of a memory phenotype. One aspect of the invention relates to the use of said cells in anti-tumour treatment comprising the combined administration of said mesenchymal stem cells with anti-tumour immunotherapies, such as checkpoint inhibitors, immune cells, for example T cells, such as T cells with artificial T cell receptors, for example a chimeric antigen receptor (CAR-Ts) or exogenous T-Cell Receptor (TCR) transduced cells, NK cells or macrophages / monocytes, or a cancer vaccine.

Description

technical field [0001] The present invention relates to genetically modified mesenchymal stem cells (MSCs), and their use as a drug for treating tumors, said MSCs comprising one or more exogenous nucleic acid molecules, wherein said exogenous nucleic acid molecules include A region of a promoter or promoter / enhancer combination encoding one or more immune response stimulating cytokines or immune response modulating cytokines. The present invention further relates to genetically modified mesenchymal stem cells comprising at least one exogenous nucleic acid molecule comprising a region encoding an immunostimulatory molecule that induces, for example, T cell proliferation and / or differentiation. [0002] The present invention encompasses the use of MSCs as a medicament for the treatment of tumors and / or neoplastic diseases, for example by modulating the tumor microenvironment to attract immune effector cells and promote the activation of said immune effector cells and / or the adop...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/28C07K14/52C12N5/0775A61P35/00
CPCA61K35/28C07K14/52C12N5/0663C12N2510/02A61K38/00A61K2035/124A61P35/00A61P43/00A61K35/17C07K14/54C07K14/555C07K14/70521C07K16/30
Inventor 克里斯蒂安·根特尔斯特凡诺斯·泰奥哈里斯费利克斯·赫尔曼拉尔夫·哈斯
Owner APCETH GMBH & CO KG
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