Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und Umwelt

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

Max-delbrueck-centrum Fuer Molekulare Medizin

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

Max-delbrück-centrum Für Molekulare Medizin in Der Hemlholtz-gemeinschaft

Max-delbrück-centrum Für Molekulare Medizin in Der Helmholtz-gemeinshcaft

Max-delbrück-centrum Für Molekulare Medizin in Der Helmholtz-geminschaft

Zentrum München-deutsches Forschungszentrum Für Gesundheit Und Umwelt (gmbh)

Max-delbruck-centrum Fur Molekulare Medizin

Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Fuer Gesundheit Und Umwelt Gmbh

Deutsches Rheuma-forschungszentrum Berlin

Max-delbruck-centrum Fur Molekulare Medizin Berlin-buch

Wolfgang Uckert

Dolores Schendel

Susanne Wilde

Bernhard Frankenberger

Elisa Kieback

Armin Rehm

Julia Bluhm

Stephen Marino

Christian Ellinger

Zsuzsanna Izsvák

Uta Elisabeth Höpken

Felix Lorenz

Mario Bunse

Julian Clauss

Thomas Blankenstein

Uta Höpken

Jehad Charo

Krystyna Dudaniec

Anthea Wirges

Cynthia Perez

Simon Fillatreau

Stephen Anderton

Ulrik Stervbo

Vicky Lampropoulou

Elisabeth Kieback

An isolated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a B Cell Maturation Antigen (BCMA) polypeptide. The CAR preferably binds an epitope comprising one or more amino acids of residues 13 to 32 of the N-terminus of human BCMA. Also disclosed is 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 said cell in the treatment of a medical disorder associated with the presence of pathogenic B cells, such as a disease of plasma cells, memory B cells and/or mature B cells, in particular multiple myeloma, non-Hodgkin's lymphoma or autoantibody-dependent autoimmune diseases.

Chimeric antigen receptor and CAR-T cells that bind BCMA

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 invention relates to an isolated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a B Cell Maturation Antigen (BCMA) polypeptide. The CAR preferably binds an epitope comprising one or more amino acids of residues 13 to 32 of the N-terminus of human BCMA. 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 said cell in the treatment of a medical disorder associated with the presence of pathogenic B cells, such as a disease of plasma cells, memory B cells and/or mature B cells, in particular multiple myeloma, non-Hodgkin's lymphoma or autoantibody-dependent autoimmune diseases.

The present invention relates to the field of genetic engineering, in particular, to a transposon-based transfection kit suitable for transfection of primary cells, such as T cells, comprising mRNA encoding a transposase, or reagents for generating mRNA encoding said transposase, as well as minicircle DNA comprising the transposon. The invention also relates to a nucleic acid, preferably, a DNA minicircle, comprising a transposon, wherein the transposon encodes a protein and at least one miRNA, wherein the sequences encoding the miRNA are located in an intron and expression of the protein and the miRNA is regulated by the same promoter. The invention also provides a population of cells obtainable with the method of the invention. Methods of transfection are also provided, as well as medical use, e.g. in immunotherapy, in particular, in adoptive T cell therapy or T cell receptor (TCR) or chimeric antigen receptor (CAR) gene therapy.

Transposon-based transfection system for primary cells

An isolated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a human CXC chemokine receptor type 5 (CXCR5) protein. Also disclosed is 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 said cell in the treatment of a medical disorder associated with the presence of pathogenic cells expressing CXCR5, preferably pathogenic mature B cells and/or memory B cells, and/or pathogenic T cells and/or T follicular helper cells, in particular mature B cell non-Hodgkin's lymphoma (B-NHL), T cell non-Hodgkin's lymphoma, or autoantibody-dependent autoimmune disease, preferably selected from systemic lupus erythematosus (SLE) or rheumatoid arthritis.

Chimeric antigen receptors and CAR-T cells that bind CXCR5 and methods of use thereof to treat medical disorders

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 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

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

Growing community of inventors

Berlin, Germany

Wolfgang Uckert