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A German university developed a cancer therapy strategy based on a carbohydrate antigen GD2 target upregulation by an enhancer of zeste homolog 2 (EZH2) EZH2 inhibition. This development responds to the need for improved therapies in GD2 low or GD2neg cancers. The university offers license agreements to industrial partners.
Chimeric antigen receptors (CARs) are recombinant proteins that redirect immune effector cells (T cells, NK cells) to tumor-associated antigens. CAR-modified T cells have powerful therapeutic activity against B cell malignancies. The development also for solid tumors is limited by the paucity of target antigens reliably expressed on the cell surface of cancer cells but not normal cells. One candidate antigen is the carbohydrate antigen GD2 , since it is aberrantly overexpressed in various cancers including neuroblastoma, osteosarcoma, ewing sarcoma, melanoma and breast cancer.
The obstacle for effective GD2-directed immune therapeutics in cancer is heterogeneous expression of GD2 on tumor cells, often below the detection threshold for GD2–specific CARs or antibodies, resulting in immune escape. Moreover, not all cancers of the above entities are GD2-positive. There is an urgent need for improved therapies in GD2 low or GD2 neg cancers or subpopulations thereof. The technical problem is to comply with this need.
The present invention of a German university relates an inhibitor for use in a method of treating a solid tumor in a subject, wherein the method further comprises the administration of a GD2-specific CAR-T cell or CAR-NK cell or a GD2 specific antibody to the subject. Further, the present invention relates to a GD2-specific CAR-T cell or CAR-NK cell or a GD2-specific antibody for use in a method of treating a solid tumor in a subject, wherein (i) the method further comprises the administration of an EZH2 inhibitor to the subject; and/or (ii) the subject has been and/or is treated with an EZH2 inhibitor. Additionally, the present invention relates to methods for increasing the surface expression of GD2 in solid tumor cells and kits and kits of-part comprising an EZH2 inhibitor and a GD2-specific CAR-T cell or CAR-NK cell or a GD2-specific antibody.
Partners from pharmaceutical industry are sought for license agreements. Within the agreements there are opportunities for further development and commercial use.
• A novel combined epigenetic and immunological strategy for improved cancer therapy is created.
• GD2neg cancers become targetable by GD2 directed immune therapeutics.
• Preventing immune escape of GD2 low tumor cells develops GD2-directed immune therapeutics to their full potential.
The university offers license agreements
Type of partner sought: Pharmaceutical industry
Role of partner: Make use of the invention, further develop the invention and integrate it in cancer therapy