Johannes Gutenberg-Universität Mainz

Biontech Rna Pharmaceuticals Gmbh

Universitaet Duisburg-essen

Universitaetsmedizin Der Johannes Gutenberg-universitaet Mainz

Martina Fatho

Volker Lennerz

Thomas Woelfel

Annette Paschen

Daniela Eberts

Hakim Echchannaoui

Dirk Schadendorf

Catherine Woelfel

Pierre Van Der Bruggen

Thomas Wolfel

Silke Luebcke

Emmanuelle Wesarg

Thomas Wölfel

Serena Debo

Silke Lübcke

Anette Paschen

Silke LÜBCKE

Chris Schmidt

Catherine Wölfel

The present invention relates to novel tumor-associated antigens, which elicit independently from a presentation via MHC a CD8-positive T-cell response. GM-CSF-Receptor alpha chain (CSF2RA) and Tyrosinase-related protein 2 (TRP-2) were found to be targets of CD8-positive T-cell clones which could detect the proteins on the surface of HLA I negative melanoma cells. Thus, the invention provides proteins, protein fragments and polypeptides of the novel antigens for use in medicine, for example for the treatment, diagnosis and prevention of a tumor disease. Furthermore provided are nucleic acids expressing the antigens of the invention, binding agents specific for the antigens of the invention, such as T-cell receptor chains and isolated T cells which are reactive against the antigens of the invention or which express the T-cell receptors of the invention. The invention further pertains to pharmaceutical compositions, especially vaccine compositions, comprising the antigens, nucleic acids, binding agents or T cells in accordance with the invention, and methods for the generation of T cells, which are specifically reactive to the antigens of the invention in an MHC-independent manner.

MHC-independent tumor-associated antigens

T cell receptors with MHC independent binding to GM-CSF receptor alpha chain

The present invention relates to a method for identifying the preferential target antigens of antitumoural T-cells of a tumour patient, comprising: a) providing T-cells from the blood of at least one tumour patient, b) providing dendritic cell (DCs) and/or B-lymphocytes (BLCs) that are autologous for said tumour patient, wherein said DCs and BLCs were transfected beforehand with a selection of mRNAs encoding for T-cell-immunogenic tumour-associated antigens (TAA), and express these, c) contacting said T-cells with the DCs and/or BLCs, d) identifying of those T-cells that recognize antigens of the DCs and/or BLCs, and e) identifying of the preferential target antigens of antitumoural T-cells of the at least one tumour patient on the basis of the T-cells that recognize antigens of the DCs and/or BLCs. The method can furthermore comprise the expansion of the T-cells that recognize the antigens of the DCs and/or BLCs. The present invention furthermore relates to a method for producing an individualized tumour vaccine or individualized tumour therapeutic, as well as corresponding methods for treating a tumourous disease using the individualised tumour vaccine or individualised tumour therapeutic.

Detection of individual T-cell reaction patterns against tumor-associated antigens (TAA) in tumor patients as a basis for the individual therapeutic vaccination of patients

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Woerrstadt, Germany

Martina Fatho