Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und Umwelt

Medigene Immunotherapies Gmbh

Max-delbrueck-centrum Fuer Molekulare Medizin

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

Roche Diagnostics Gmbh

Helmholtz Zentrum Muenchen Deutsches Forschungzentrum Fuer Gesundheit Und Umwelt Gmbh

Helmholtz Zentrum München Deutsches Forschungszentrum Für Gesundlheit Und Umwelt (Gmbh)

Helmholtz Zentrum München Deutsches Forschungszentrym Für Gesundheit Und Umwelt (Gmbh)

Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und

Zentrum München-Deutsches Forschungszentrum Für Gesundheit Und Umwelt (Gmbh)

Max-delbruck-centrum Fur Molekulare Medizin

Max-delbruck-centrum Fur Molekulare Medizin Berlin-buch

Dolores Schendel

Wolfgang Uckert

Christian Ellinger

Susanne Wilde

Slavoljub Milosevic

Carina Wehner

Bernhard Frankenberger

Rudolf Wank

Elfriede Noessner

Anke Zobywalski

Iris Bigalke

Elisabeth Weiss

Christine Falk

Felix Lorenz

Winfried Albert

Thomas Blankenstein

Josef Endl

Peter Stahl

Tanja Herrmann

Stefani Spranger

Manon Weis

Daniel Krappmann

Daniel Nagel

Guenther-Gerhard Jung

Michaela Kügler

Edgar Meinl

Klaus Dornmair

The present invention relates to the field of immunotherapy, in particular, to adoptive T cell therapy, T cell receptor (TCR) gene therapy and vaccination. The invention provides a method for preparing a nucleic acid encoding the TCR alpha chain construct (TRA) and TCR beta chain construct (TRB) of a TCR construct specific for an epitope from an antigen presented on major histocompatibility complex (MHC), comprising contacting T cells isolated from a donor with a library of artificial antigen presenting cells (APC) comprising cells expressing all MHC I or MHC II alleles present in the donor, preferably, in K562 cells. The TCR construct can be expressed in a T cell, which is useful for adoptive T cell therapy, e.g., of cancer, viral infections or autoimmune diseases. The invention further provides a method for identifying the epitope recognized by said TCR. Immunogenic epitopes recognized by said TCRs can be used to develop vaccine formulations to induce antigen-specific T cell immunity in patients. The invention further provides pairs of two TCR constructs and respective immunogenic epitopes obtained by the method of the invention, wherein the epitopes are from human papillomavirus (HPV) 16 (also designated alphapapillomavirus 9) oncoprotein E5 and human cytomegalovirus (CMV) protein pp65.

Method of detecting new immunogenic T cell epitopes and isolating new antigen-specific T cell receptors by means of an MHC cell library

The present invention relates to the field of biotechnology. Specifically, the invention provides antigen-specific T-cell receptors (TCRs). Further, the invention encompasses polynucleotides encoding the same and vectors comprising said polynucleotides. Host cells comprising the molecules of the invention are also provided. Moreover, the invention provides means and methods for diagnostics and therapy, in particular of cancer.

T cell receptors and uses thereof

The invention relates to a method for generating an antibody binding to a cell surface protein of interest, the method comprising the following steps:

Method for generating antibodies against T cell receptor

The present invention contemplates methods for the generation of human antigen-specific T lymphocytes. The methods employ MHC class-II targeting signals fused to an antigen or fragment thereof to obtain MHC class presentation of RNA coded proteins. Accordingly, the present invention concerns expression vectors comprising MHC class-II targeting signal and at least one antigen or fragment thereof and its use for the in vitro generation of antigen-specific T lymphocytes. T cell clones and T cell receptors (TCRs) specific for tumor antigens or viral antigens are also described.

Generation of antigen-specific TCRs

The present invention contemplates dendritic cell compositions. The dentritic cell compositions employ MHC class-II targeting signals fused to an antigen or fragment thereof to obtain MHC II presentation of the antigen or fragment thereof. In particular, the invention refers to a dendritic cell vaccine comprising dendritic cells expressing a MHC class-II targeting signal fused to an antigen or fragment thereof. Dendritic cell vaccines for the stimulation of an immune response against melanoma-associated antigen are also described.

Dendritic cell composition

The invention relates to a library for the expression of all functional TCR types comprising 45 TCR constructs each encoding one of the 45 different TCR &#x3b1; chains and 47 TCR constructs each encoding one of the 47 different TCR &#x3b2; chains, wherein each of the 45 TCR constructs encoding one of 45 different TCR &#x3b1; chain comprises the following building blocks one of the variable AV segments AVseg1 to AVseg45, and a constant AC segment, and wherein each of the 47 TCR constructs encoding one of 47 different TCR &#x3b2; chains comprises one of the variable BV segments BVseg1 to BVseg47, and a constant BC segment.

T cell receptor library

The present invention is directed to a high affinity T cell receptor (TCR) against a tumor-associated antigen, an isolated nucleic acid molecule encoding the same, a T cell expressing the TCR, and a pharmaceutical composition for use in the treatment of diseases involving malignant cells expressing the tumor-associated antigen.

High affinity T cell receptor and use thereof

The present invention is directed to a high affinity T cell receptor (TCR) against a tumor-associated antigen, an isolated nucleic acid molecule encoding same, a T cell expressing said TCR, and a pharmaceutical composition for use in the treatment of diseases involving malignant cells expressing said tumor-associated antigen.

The present invention relates to semi-allogeneic antigen-presenting cells into which proteins and/or peptides or RNA or DNA or cDNA, respectively, encoding said proteins and/or peptides which are overexpressed in tumor cells or which are derived from autologous tumor cells or different tumor cells or different tumor cell lines have been introduced. Furthermore the invention relates to methods for the generation of these semi-allogeneic antigen-presenting cells as well as to the use thereof in the treatment of tumor diseases.

Semi-allogenic anti-tumour vaccine with HLA haplo-identical antigen-presenting cells

The invention relates to a method for in vitro maturation of at least one immate dendritic cell, comprising stimulating said immature dendritic cell with TNF&#x3b1;, IL-1&#x3b2;, IFN&#x3b3;, a TLR7/8 agonist and prostaglandin E2(PG). Furthermore, the invention elates to a composition comprising these factors as well as to mature dendritic cells produced by a method of the invention.

Compositions for the preparation of mature dendritic cells

The invention relates to a compound for use in treating a cancer, wherein the cancer depends on the proteolytic activity of the MALT1 protease, and wherein the compound has the general formula (I) wherein X is N or C; Y is S, O, SO, SO, NH, CO, CH, CH&#x2550;CH, or CH&#x2014;CH; ( )is a C-Clinear or branched alkyl chain; A is NRR, or OR, or HET; Rand Rin each occurrence are independently selected from &#x2014;H, &#x2014;CH, &#x2014;OH, &#x2014;OCH, &#x2014;SCH, &#x2014;F, &#x2014;Cl, &#x2014;CF, &#x2014;NH, and &#x2014;COOH; R, R, and Rare H, or C-Clinear or branched alkyl groups, and HET is a heterocyclic ring of 5, 6, or 7 members, wherein the ring atoms can be C, O, N, or S, the ring can be saturated or aromatic, and the ring can be substituted with H or C-Clinear or branched alkyl groups; or a pharmaceutically acceptable salt, prodrug, enantiomer, diastereomer, racemic mixture, crystalline form, amorphous form, unsolvated form or solvate of said compound. The compound of the invention may further be used in the treatment of MALT1-dependent immune diseases.

Selective inhibition of MALT1 protease by phenothiazine derivatives

The present invention is directed to a kit-of-parts or composition containing nucleic acid sequences coding for high-avidity, allo-restricted TCR, wherein the TCR are independently directed against the tyrosinase antigen, the melan-A antigen and the survivin antigen. The invention is further directed to a kit-of-parts or composition containing at least three groups of transgenic lymphocytes transformed with vectors coding for TCR against said antigens. Furthermore, the present invention provides a pharmaceutical composition and its use in the treatment of diseases involving malignant cells expressing said tumor-associated antigens. The invention further relates to a nucleic acid molecule coding for a TCR that recognizes the survivin antigen, a TCR encoded thereby and a T cell expressing said TCR. Further, the invention discloses a vector, a cell and a pharmaceutical composition encoding/containing same and their use in the treatment of diseases involving malignant cells expressing survivin.

Repertoire of allo-restricted peptide-specific T cell receptor sequences and use thereof

Growing community of inventors

Munich, Germany

Dolores Schendel