Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und Umwelt

Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt Gmbh

Elfriede Noessner

Dolores Schendel

Christine Falk

Elisabeth Weiss

Ramona Schlenker

Stephan Weisz

The present invention relates to fusion proteins comprising (a) an extracellular domain containing a polypeptide derived from PD-1 or CD40L at its N-terminus; (b) a transmembrane domain; and (c) an intracellular domain containing a polypeptide derived from 4-1BB or CD28 at its C-terminus. Also, fusion proteins with CD28 at the N-terminus and CD40L at the C-terminus are envisaged. The present invention also relates to nucleic acid molecules encoding such fusion proteins, vectors containing such nucleic acid molecules, and host cells containing such vectors. The present invention further relates to methods for producing such host cells. Finally, the present invention relates to pharmaceutical compositions comprising such fusion proteins, nucleic acid molecules, vectors, and/or host cells, particularly for treating diseases or disorders associated with PD-1/PD-L2 or CD40 binding and/or PD-L1/PD-L2 or CD40 expression such as cancer and chronic viral infection.

Fusion proteins of PD-1 and 4-1BB

This invention is directed to therapeutic compositions containing non-MHC-restricted Tcells/NK-cells in combination with MHC-restricted T-cells and especially to therapeutic compositions, which comprise LAK cells. Furthermore, the present invention is directed to the use of the above combination in the treatment of tumors in humans, which tumors show a missing, low or aberrant expression of MHC class Ia or Ib molecules. By using the aforementioned compositions/combinations it is possible to provide a balanced selective pressure against emergence of tumor cell variants that would otherwise escape immune detection.

Attack of tumor cells with missing, low or aberrant MHC expression by combining non MHC-restricted T-cells/NK-cells and MHC-restricted cells

This invention is directed to therapeutic compositions containing non-MHC-restricted T-cells/NK-cells in combination with MHC-restricted T-cells and especially to therapeutic compositions, which comprise LAK cells. Furthermore, the present invention is directed to the use of the above combination in the treatment of tumors in humans, which tumors show a missing, low or aberrant expression of MHC class 1a or 1b molecules. By using the aforementioned compositions/combinations it is possible to provide a balanced selective pressure against emergence of tumor cell variants that would otherwise escape immune detection.

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Munich, Germany

Elfriede Noessner