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Publication Number

US-12655394-B2

Patent

Publication Date

2026-06-16

Expiration Date


Abstract

The present invention relates to a method for the production of a culture, e.g. an organoid culture of ovarian cancer or cancer precursor cells, particularly of high grade serous ovarian carcinoma cells. By means of this method, an organoid culture of ovarian cancer or cancer precursor cells and a biobank comprising a plurality of different organoid cultures of ovarian cancer or cancer precursor cells may be generated. Further, a culture medium suitable for the long-term culture of ovarian cancer or cancer precursor cells is provided. Furthermore, use of the organoid culture and the biobank for medical applications, e.g. in the field of diagnostics, and therapy and in the field of drug screening is described.

Core Innovation

The invention relates to a method for the production of an ovarian cancer or cancer precursor cell organoid culture. The method comprises isolating ovarian cancer or cancer precursor cells obtained from a human patient with ovarian carcinoma and cultivating the cells in a cell culture medium to obtain an organoid cell culture.

The cell culture medium stimulates Bone Morphogenetic Protein (BMP) signaling through at least one compound and includes at least one compound selected from a group comprising a serum-free neuronal supplement, nicotine amide, a ROCK inhibitor, an N-2 supplement and a TGFβ inhibitor. The medium is free of Noggin and free from exogenously added Wnt protein.

Two defined medium variants are described that include EGF and BMP2, or EGF together with FGF and Rspondin. The invention is directed to maintaining and propagating patient-derived ovarian cancer or cancer precursor cell organoid cultures under these BMP-stimulating, Noggin-free, and exogenously Wnt-protein-free conditions.

Claims Coverage

The provided partial content includes one independent claim covering two inventive features: production of ovarian cancer or cancer precursor cell organoid cultures in a BMP-signaling stimulating medium that is free of Noggin and free from exogenously added Wnt protein, and isolation of patient-derived cells followed by cultivation to obtain and further culture the organoid cell culture.

BMP-signaling medium for organoid production without Noggin or exogenous Wnt

A method for the production of an ovarian cancer or cancer precursor cell organoid culture using a cell culture medium that stimulates Bone Morphogenetic Protein (BMP) signaling, includes at least one compound selected from a serum-free neuronal supplement, nicotine amide, a ROCK inhibitor, an N-2 supplement and a TGFβ inhibitor, and is free of Noggin and free from exogenously added Wnt protein.

Patient-derived isolation and organoid culture workflow

The method comprises isolating ovarian cancer or cancer precursor cells obtained from a human patient with ovarian carcinoma, obtaining an organoid cell culture from the cultivation step, and culturing the organoid cell culture.

Overall, the claim content centers on patient-derived ovarian cancer or cancer precursor cell organoid cultures produced and maintained in a Noggin-free, exogenous Wnt-protein-free BMP-stimulating medium, with defined EGF/BMP2 or EGF/FGF/Rspondin variants.

Stated Advantages

The organoid cultures can be expanded long-term as stable organoids.

The organoids recapitulate biomarker/phenotype/genomic features.

The organoids show drug response heterogeneity for testing.

The organoids can be frozen and thawed for biobanking.

The organoids can be expanded to multiwell formats for high-throughput testing.

The organoids support patient-specific testing, including platinum-chemotherapy efficacy testing.

The organoids are described as usable for immunotherapy-related testing, including T-cell assays and neoantigen identification.

Documented Applications

Diagnostics/therapy using patient-derived ovarian cancer organoid cultures.

Drug screening and patient-specific treatment guidance, including platinum-chemotherapy efficacy testing.

Immunotherapy testing, including T-cell assays and neoantigen identification.

Biobanking using freezing and thawing of organoid cultures.

High-throughput testing using multiwell formats.

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