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

a technology of immune response and cytokine, which is applied in the field of genetically modified mesenchymal stem cells expressing immune response-stimulating cytokine to attract and/or activate immune cells, and achieves the effect of reducing the level of unwanted side effects

Inactive Publication Date: 2017-08-24
APCETH GMBH & CO KG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a new way to treat cancers using immunotherapy. It offers means to stimulate the immune system specifically against tumor tissue. This allows for the effective treatment of cancer while minimizing harmful side effects.

Problems solved by technology

In particular, a problem underlying the invention is the provision of suitable means for local stimulation of an immune response directed against tumour tissue in a subject.

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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examples

[0206]The following examples are presented in order to describe practical and in some cases preferred embodiments of the invention, by demonstrating a practical implementation of the invention, without being limiting to the scope of the invention or the concepts described herein.

[0207]Experimental Models:

[0208]Mesenchymal stem cells can be extracted according to either Lange C. et al. (“Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine”, J. Cell Physiol. 2007, Apr. 25) or Soleimani (“A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow”, Nat Protoc. 2009;4(1):102-6).

[0209]The cells grow adherently and continuously in cell culture. MSCs may be transformed with retroviral or lentiviral vectors comprising cytokine encoding gene sequences. Viral constructs can be engineered according to standard protocols and produced that express genes encoding IL-2, IL-7, IL-15, I...

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Abstract

A genetically modified mesenchymal stem cell (MSC) and medical use thereof in the treatment of tumors, the MSC including one or more exogenous nucleic acid molecule(s), wherein the exogenous nucleic acid molecule(s) include 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 the cells in modulating the tumor 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 the cells in anti-tumor treatment including combined administration of the mesenchymal stem cells with anti-tumor 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

[0001]The invention relates to a genetically modified mesenchymal stem cell (MSC), and their use as a medicament in the treatment of a tumour, said MSCs 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 further relates to a genetically modified mesenchymal stem cell comprising at least one exogenous nucleic acid molecule that comprises a region encoding an immune stimulatory molecule, for example that that induces T-cell proliferation and / or differentiation.[0002]The invention encompasses the use of MSCs as a medicament in the treatment of a tumour and / or tumour disease, for example by modulating the tumour microenvironment in order to attract immune effector cells and facilitate their activation and / or adoption of a memory phenotype. One aspe...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/28C07K16/30C07K14/705A61K35/17C07K14/54C07K14/555
CPCA61K35/28C07K14/54C07K14/555A61K2035/124A61K35/17C07K16/30A61K38/00C07K14/70521C07K14/52C12N5/0663C12N2510/02A61K39/461A61K39/4631A61K2239/31A61K39/464499A61P35/00A61P43/00
Inventor GUNTHER, CHRISTINETHEOHARIS, STEFANOSHERMANN, FELIXHUSS, RALF
Owner APCETH GMBH & CO KG
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