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

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...

AI Technical Summary

Benefits of technology

[0007]In light of the prior art the technical problem underlying the present invention is to provide a novel strategy for immunotherapy of cancers. 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. A further problem underlying the invention is the provision of means for administration of an effective dose of therapeutic agents, such as immune modulatory or immune stimulatory agents, that provides an effective local effect at the target tissue with reduced levels of unwanted 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.

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