Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und Umwelt

Gsf-forschungszentrum Fur Umwelt Und Gesundheit, Gmbh

Medizinische Hochschule Hannover

Gsf Forshungszentrum Fur Umwelt Und Gesundheit Gmbh Ingolstradter

Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und Umwelt (gmb)

Ludwig-Maximilians-Universitat München

Wolfgang Hammerschmidt

Dagmar Pich

Reinhard Zeidler

Henri-Jacques Delecluse

Georg W Bornkamm

Renata Stripecke

Axel Polack

Bettina Kempkes

Martin Staege

Gilbert Reisbach

Sibille Humme

Ursula Zimber-Strobl

Romana Ruiss

Aloys Schepers

Constanze Slabik

The present invention provides herpesviruses, such as EBV, which lack at least one viral miRNA. Such herpesviruses lacking at least one viral miRNA are advantageously not capable of packaging their genome into the capsid, thereby producing HVLPs, which are substantially free of their herpesvirus genome or the nucleic acid molecule encoding the proteinaceous part of the HVLP and viral miRNA. Such HVLPs may be used as vaccine.

Means and methods for treating herpesvirus infection

An isolated chimeric antigen receptor (CAR) polypeptide, wherein the CAR includes an extracellular antigen-binding domain, including an antibody or antibody fragment that binds to a protein encoded by a herpes virus, or to a protein complex including the protein (herpes virus antigen), wherein the herpes virus antigen is present on the surface of a human cell that is latently infected with said herpes virus and supports the lytic phase of viral replication. The invention further relates to a nucleic acid molecule encoding the CAR of the invention, a genetically modified immune cell, preferably a T cell, expressing the CAR of the invention and the use of the cell in the treatment of a medical disorder associated with human herpesvirus, such as herpes virus-associated cancers, chronic active herpes virus infections or primary herpes virus infections. In preferred embodiments the herpes virus is Epstein-Barr virus (EBV) and a preferred herpes virus antigen target of the CAR is the EBV glycoprotein 350/220 (gp350/gp220).

Chimeric antigen receptor and CAR-T cells that bind a herpes virus antigen

The present invention relates to a vaccine comprising a particle, said particle comprising (i) at least one Epstein-Barr virus (EBV) structural polypeptide, (ii) at least one EBV lytic polypeptide, (iii) membrane lipids, said particle being devoid of EBV DNA, wherein (a) the B-cell transformation capacity of one or more EBV polypeptides required for B-cell transformation as comprised in said particle is disabled while their immunogenicity is maintained; and or (b) said particle is devoid of one or more EBV polypeptides required for B-cell transformation. Furthermore, the invention relates to a method for generating a particle, to a cell obtained in the method of the invention, a kit comprising the vaccine or the particle generated according in the method of the invention. Also, the invention relates to the use of the vaccine or the particle generated according to the method of the invention for generating CD8+ cells specific for an EBV antigen.

Epstein-Barr-virus vaccine

The present invention is directed to a conditional gene vector system and to a host cell, which has been transfected with such a vector system. The present invention is further directed to a combined preparation comprising the vector system of the invention and an interfering agent. Furthermore, a pharmaceutical composition and its use in the treatment of hemophilia, diabetes, rheumatoid arthritis, genetic immunodeficiency, and graft versus host disease is provided.

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The present invention relates to a method for helper virus-free packaging of gene vector DNA into the virus particles of a DNA virus as well as to eukaryotic helper cells for helper virus-free packaging of gene vector DNA into the virus particles of a DNA helper virus wherein a DNA virus having a genome &gE;100 kbp is employed (FIG. 1).

Method for helper virus-free packaging of a gene vector DNA

The invention relates to a method for the preparation of DNA virus vectors capable of replication in eukaryotic as well as in prokaryotic cells as well as to DNA virus vectors prepared by this method. Preferably, the method is used to prepare Epstein-Barr virus vectors.

DNA virus vectors and methods for their preparation

T cells having a desired antigen specificity are stimulated by (a) introducing immortalizing genes into antigen-presenting cells in a manner permitting regulation of the expression and/or function of at least one of these genes to achieve conditionally immortalized antigen-presenting cells; (b) introducing a gene encoding the desired antigen into the immortalized cells in a manner permitting the antigen to be expressed after the expression and/or abolishment of the function of at least one of the immortalizing genes stops; (c) expanding the immortalized antigen-presenting cells by expression and/or functional activation of the immortalizing genes; (d) completing the proliferation of the immortalized antigen-presenting cells by stopping the expression and/or abolishing the function of at least one of the controllable immortalizing genes; (e) continuing the expression of the antigen; (f) adding leucocytic cells including T cells and cultivating the cell mixture to stimulate the T cells directed against the desired antigen; and (g) optionally purifying and isolating the stimulated T cells.

Method for the stimulation of T cells having a desired antigen specificity

Growing community of inventors

Munich, Germany

Wolfgang Hammerschmidt