Max-delbruck-centrum Fur Molekulare Medizin (mdc) Berlin-buch

Max-delbrueck-centrum Fuer Molekulare Medizin

Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und Umwelt

Max-delbruck-centrum Fur Molekulare Medizin

Max-delbruck-centrum Fur Molekulare Medizin in Der Helmholtz-gemeinschaft

Max-delbrück-centrum Für Molekulare Medizin in Der

Max-delbrueck-centrum Fuer Molekulare Medizin in Der Helmholtz-gemeinschaft

Max-delbrüeck-centrum Für Molekulare Medizin (mdc) Berlin-buch

Helmholtz-gemeinschaft; Charité—universitätsmedizin Berlin

Charité – Universitätsmedizin Berlin

Max-delbruck-centrum Fur Molekulare Medizin Berlin-buch

Thomas Blankenstein

Matthias Obenaus

Catarina Leitão

Jehad Charo

Gerald Willimsky

Dolores Schendel

Wolfgang Uckert

Susanne Wilde

Elisa Kieback

Antonio Pezzutto

Lucia Poncette

Xiaojing Chen

Catarina Leitâo

Sophie Cayeux-Pezzutto

Simone Rhein

Catarina Leitao

Elisabeth Kieback

Cynthia Perez

The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer, in particular, of B cell lymphoma or B cell leukemia. The invention provides a nucleic acid encoding TCR alpha or beta chain constructs of TCR constructs capable of specifically binding to a peptide of SEQ ID NO: 1, derived from the lineage specific antigen CD22, in the context of HLA-A2 and to subsequently lyse CD22-positive cells. The invention further provides a corresponding protein and host cell. e.g., a CD8+ T cell, pharmaceutical compositions comprising the same, and therapeutic use for treatment of B cell lymphoma or B cell leukemia, such as diffuse large B-cell lymphoma (DLBCL).

CD22-specific T cell receptors and adoptive T cell therapy for treatment of B cell malignancies

The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells—such as CD4 or CD8 positive T cells—which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new approaches for immune therapy, specifically adoptive T cell therapy, for treating cancer.

High avidity antigen recognizing constructs

The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells&#x2014;such as CD4 or CD8 positive T cells&#x2014;which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new approaches for immune therapy, specifically adoptive T cell therapy, for treating cancer.

The present invention pertains to novel high avidity antigen recognizing constructs against Human Papilloma Virus antigens. The invention provides novel T cell receptor (TCR) based molecules which are selective and specific for HPV 16/18 proteins E5, E6 and E7. The TCR of the invention, and HPV antigen-binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of HPV infection, as well as for the diagnosis, treatment and prevention of HPV infection mediated secondary diseases as HPV infection caused cancers, such as cervical, nasopharyngeal or head and neck cancer. Further provided are nucleic acids encoding the proteins of the invention, and recombinant cells expressing the same.

High avidity HPV T-cell receptors

The present invention relates to the field of immunotherapy, in particular adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides a nucleic acid encoding at least one T cell receptor alpha chain construct and/or TCR beta chain construct of a TCR construct capable of specifically binding to an epitope from NY-ESO-1 (also designated CTAG-1) in complex with a human MHC, wherein the TCR alpha chain construct and/or the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having at least 90% sequence identity to an amino acid selected from SEQ ID NO: 1-20. The invention provides TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC I, and, for the first time, TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC II molecules, and thus enables a combined adoptive T cell therapy with both recombinant CD4+ and re-combinant CD8+ T cells. The invention also provides proteins and host cells corresponding to said TCR constructs, as well as the medical use of such constructs, in particular, in the diagnosis, prevention, and/or treatment of a proliferative or viral disease, wherein, preferably, both TCR constructs restricted to MHC I and MHC II molecules are provided in a kit. The invention also relates to a mouse transgenic for the human TCR loci and human HLA-DR4, ABabDR4 mouse.

Combined T cell receptor gene therapy of cancer against MHC I and MHC II-restricted epitopes of the tumor antigen NY-ESO-1

The present invention relates to a method for the production of novel T-cell receptors (TCR) which provide a reduced risk of adverse events in immune therapy, specifically in adoptive T cell transfer. The TCRs produced according to the method of the invention are specific for tumor cells and do not react with healthy tissue. Furthermore provided are nucleic acids encoding the TCR of the invention, vectors and host cells comprising the TCRs of the invention as well as their use is the treatment of tumorous diseases.

Tumor specific T-cell receptors

The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells&#x2014;such as CD4 or CD8 positive T cells&#x2014;which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new means for immune therapy, specifically adoptive T cell therapy, for treating cancer.

The present invention relates to a method for selecting a host cell population expressing a functional fusion protein comprising at least one epitope-providing amino acid sequence (epitope-tag) and the amino acid sequence of a protein that is expressed on the surface of said host cell. Preferably, the amino acid sequence comprises an alpha or beta chain of a T-cell receptor. The present invention further relates to uses of said functional T-cell receptor (TCR) alpha or beta chain fusion protein in medicine, in particular in adoptive transfer.

Epitope-tag surface expressed proteins and nucleic acids thereof

The present invention relates generally to the field of molecular biology. More specifically, the present invention relates to expression systems for use in modulating the expression of protein coding target genes in vivo or in vitro. More specific, this invention relates to RNA polymerase III-based methods and systems for expression of therapeutic proteins in cells in vivo or in vitro.

Use of Pol III promoters for controlled expression of therapeutic proteins

The present invention is directed to a method of generating antigen specific T cells. Furthermore, the invention is directed to antigen specific T cells, isolated transgenic TCR's, pharmaceutical compositions containing same and their use in adoptive cell therapy. This invention in particular pertains to the use of cells co-expressing allogeneic MHC molecules and antigens to induce peptide-specific T cells from non-selected allogeneic T cell repertoires.

Growing community of inventors

Berlin, Germany

Thomas Blankenstein