Ucl Business Plc

Imperial Innovations Limited

Ganymed Pharmaceuticals Ag

Imperial College Innovations Limited

Universitätsmedizin Der Johannes Gutenberg-Universitat Mainz

Hans Josef Stauss

Shao-An Xue

Liquan Gao

Jenny L McGovern

Ralf-Holger Voss

Matthias Theobald

Sharyn Thomas

Fiyaz Mohammed

Ben Willcox

Graham P Wright

Max Topp

The present invention relates to an engineered regulatory T cell (Treg) comprising a T cell receptor (TCR) which is capable of specifically binding to a myelin basic protein (MBP) peptide or variant or fragment thereof when the peptide is presented by a major histocompatibility complex (MHC) molecule. The present invention further relates to methods for providing an engineered Treg and to methods and uses of said engineered Treg and vectors and kits of vectors encoding said Treg.

Engineered regulatory T cell

The present invention relates to a method for enhancing the ability of regulatory T cells (Tregs) to suppress immune responses comprising increasing FOXP3 expression in a population of Tregs.

Method for enhancing the suppressive properties of Treg cells

TCR The present invention relates to an engineered T cell receptor (TCR). In particular, the present invention relates to methods for expression of a TCR when expressed as an exogenous TCR, to methods for selecting a TCR with high cell surface expression when expressed as an exogenous TCR and to methods for identifying residues which contribute to the cell surface expression level of a TCR. The present invention also relates to an engineered TCR which has a high level of cell surface expression when expressed as an exogenous TCR compared to the corresponding germline TCR sequence.

T cell receptor

A T cell receptor molecule (TCR) containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarity determining regions (CDRs):

Therapeutically useful molecules

A T cell receptor molecule (TCR) containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarity determining regions (CDRs): CDR1&#x3b1;: SSYSPS CDR2&#x3b1;: YTSAATL CDR3&#x3b1;: VVSPFSGGGADGLT or comprising or consisting of SPPSGGGADGLT and the beta chain portion contains three complementarity determining regions (CDRs): CDR1&#x3b2;: DFQATT CDR2&#x3b2;: SNEGSKA CDR3&#x3b2;: comprising SARDGGEG or comprising or consisting of RDGGEGSETQY, or wherein up to three amino acid residues in one or more CDRs are replaced by another amino acid residue. The invention also includes polynucleotides encoding the TCR molecules, and host cells containing the said polynucleotides. Patient derived T cells may have the polynucleotides encoding the TCR molecules introduced therein, and the engineered T cells may be introduced into the patient in order to combat a WT1-expressing malignancy.

The present invention relates to a single chain antigen recognizing construct (scARC), which is composed of stabilized variable domains by the introduction of novel disulfide bonds, in order to prevent residual mis-pairing with endogenous ARC chains. The invention further discloses a method for the design of a novel structurally stabilized scARC, the method being based on the visual inspection of the crystal structure of the underlying scARC and the selection of appropriate amino acid substitutions to generate a novel disulfide bond in the protein structure. Furthermore, the invention discloses a method for the production of a cell which expresses the scARC of the invention. Also described are nucleic acids encoding an inventive scARC, as well as DNA and RNA constructs that allow for the expression of the inventive scARC. The invention further encompasses pharmaceutical compositions containing the scARC of the invention and the use of the scARC in therapy of cancerous or infectious diseases, or for use in the quantification and/or visualization of disease associated antigens.

Single chain antigen recognizing constructs (scARCs) stabilized by the introduction of novel disulfide bonds

The present invention provides a T-cell receptor (TCR) which binds to a peptide from latent membrane protein 2 (LMP-2) from the Epstein Barr Virus (EBV) having the amino acid sequence CLGGLLTMV (SEQ ID No. 1) when presented by a major histocampatability complex (MHC) molecule. The present invention also provides a nucleotide sequence encoding such a TCR, a vector comprising such a nucleotide sequence and its use to produce a EBV-specific T-cell. The present invention also provides the use of EBV-specific T-cell for cellular immunotherapy.

T-cell receptor

The present invention provides a T-cell receptor (TCR) which binds to a peptide from the cytomegalovirus (CMV) phosphoprotein pp65 having the amino acid sequence NLVPMVATV (SEQ ID No. 1) when presented by a major histocompatability complex (MHC) molecule. The present invention also provides a nucleotide sequence encoding such a TCR, a vector comprising such a nucleotide sequence and its use to produce a CMV-specific T-cell. The present invention also provides the use of CMV-specific T-cell for cellular immunotherapy.

T-cell receptor capable of recognising an antigen from cytomegalovirus

A peptide comprising the amino acid sequence RMFPNAPYL or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence CMTWNQMNL or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence HLMPFPGPLL or a portion or variant thereof provided that the peptide is not intact human gata-1 polypeptide, and polynucleotides encoding these peptides. The peptides and polynucleotides are useful as cancer vaccines.

Immunotherapeutic methods using epitopes of WT-1 and GATA-1

A T cell receptor molecule (TCR) containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarity determining regions (CDRs): CDR1&#x3b1;: SSYSPS CDR2&#x3b1;: YTSAATL CDR3&#x3b1;: VVSPF-SGGGADGLT or comprising or consisting of SPFSGGGADGLT and the beta chain portion contains three complementarity determining regions (CDRs): CDR1&#x3b2;: DFQATT CDR2&#x3b2;: SNEGSKA CDR3&#x3b2;: comprising SARDGGEG or comprising or consisting of RDGGEGSETQY, or wherein up to three amino acid residues in one or more CDRs are replaced by another amino acid residue. The invention also includes polynucleotides encoding the TCR molecules, and host cells containing the said polynucleotides. Patient derived T cells may have the polynucleotides encoding the TCR molecules introduced therein, and the engineered T cells may be introduced into the patient in order to combat a WT1-expressing malignancy.

A peptide comprising the amino acid sequence RMFPNAPYL (SEQ ID NO:1) or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence CMTWNQMNL (SEQ ID NO:2) or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence HLMPFPGPLL (SEQ ID NO:3) or a portion or variant thereof provided that the peptide is not intact human gata-1 polypeptide, and polynucleotides encoding these peptides. The peptides and polynucleotides are useful as cancer vaccines.

A method of treating a patient with a disease wherein the patient contains diseased cells which cells contain, or are associated with, an abnormal molecule or an abnormally elevated amount of a molecule and which cells are capable of presenting at least part of said molecule on their surface by an HLA class I (or equivalent) molecule, the method comprising administering to the patient a therapeutically effective amount of cytotoxic T lymphocytes (CTL) which recognize at least part of said molecule when presented by an HLA class I (or equivalent) molecule on the surface of a cell characterized in that the cytotoxic T lymphocytes are not derived from the patient with a disease. Preferably, the CTL are derived from an individual which individual does not carry the HLA class I (or equivalent) molecule type which, in the patient, presents at least part of said abnormal molecule, or molecule abnormally elevated, contained in or associated with the disease cells of said patient.

Growing community of inventors

London, United Kingdom

Hans Josef Stauss