Oxton, United Kingdom
Oxton, United Kingdom

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Patent
Adaptimmune | Date: 2016-10-12

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC SEQ ID NO:126 peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a K_(D )for the said peptide-HLA complex of less than or equal to 1 M and/or have an off-rate (k_(off)) of 110^(3 )S^(1 )or slower.


Patent
Immunocore and Adaptimmune | Date: 2016-09-12

The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs may consist essentially of TCRs which may comprise an alpha chain variable domain from a natural repertoire and a beta chain variable domain from a natural repertoire, wherein the alpha chain variable domain may comprise a TRAV12-2 or a TRAV21 gene product and the beta chain variable domain may comprise a TRBV6 gene product.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.4-4 | Award Amount: 8.26M | Year: 2012

The aim of this research is to exploit technology for nucleic acid delivery through the clinical testing of adoptive engineered T cells to treat cancer. Recent innovative developments in cancer gene-immunotherapy have led to very encouraging early clinical results. However, the use of engineered T cells is a challenging and complex field with further development and more proof-of-principle trials needed. This proposal builds upon previous EU funded pre-clinical projects and comprises a multidisciplinary and translational research group with wide-ranging relevant expertise. Building on encouraging clinical results targeting NY-ESO-1 in melanoma and the availability of clinical grade vector, the consortium proposes to rapidly initiate two landmark studies in this field: the first to examine the activity of engineered T cells in oesophago-gastric cancer as an example of a hard to treat common epithelial cancer; the second to undertake a randomised phase II study to determine whether an optimised cell production system developed by the partners improves the current clinical response rates in patients with metastatic melanoma treated with NY-ESO-1 targeted T-cells. Success in these trials will enable the consortia and others to carryout larger trials and potentially approval of this type of therapy as a treatment for multiple cancer types. The inclusion of a major industrial partner focused on cell therapy technology and two SMEs focus on the delivery of cell therapy will facilitate future development of this area following these trials; indeed the project also includes plans to further automate and streamline cell processing to facilitate this development. This project would enhance European expertise and competitiveness in an important emerging market. The research will also support the European biotechnology industry which will be important for the exploitation of these therapies and the successful outcome of this project.


Patent
Adaptimmune | Date: 2015-04-17

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC SEQ NO:126 peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a K_(D )for the said peptide-HLA complex of less than or equal to 1 M and/or have an off-rate (k_(off)) of 110^(3 )S^(1 )or slower.


Patent
Adaptimmune | Date: 2016-01-26

The present invention relates to T cell receptors (TCRs) which bind the HLA-A2 restricted FMNKFIYEI (158-166) peptide epitope derived from Fetoprotein (AFP). Certain preferred TCRs of the invention demonstrate excellent binding characteristics and specificity profiles for this AFP epitope. T cell receptors of the invention may comprise at least one TCR alpha chain variable domain and/or at least one TCR beta chain variable domain, the alpha chain variable domain which may comprise an amino acid sequence that has at least 90% identity to the sequence of amino acid residues 1-112 of SEQ ID No: 2, and/or the beta chain variable domain which may comprise an amino acid sequence that has at least 90% identity to the sequence of amino acid residues 1-112 of SEQ ID No: 3.


Patent
Adaptimmune and Immunocore | Date: 2014-04-09

A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identification of high affinity TCRs. Several high affinities are disclosed.


Patent
Immunocore and Adaptimmune | Date: 2016-02-17

The present invention provides TCRs having an affinity (K_(D)) of less than or equal to 1M, and/or an off-rate (k_(off)) of 1x10^(-3) S^(-1) or slower, for the SLYNTVATL-HLA-A*0201 complex PROVIDED THAT when the said TCR is presented by cell and comprises SEQ ID NOs: 1 and 2, the cell is not a native T cell. Such TCRs are useful, either alone or associated with a therapeutic agent, for targeting HIV infected cells presenting that complex.


Patent
Adaptimmune | Date: 2015-12-14

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC SEQ ID NO:126 peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a K_(D )for the said peptide-HLA complex of less than or equal to 1 M and/or have an off-rate (k_(off)) of 110^(3 )S^(1 )or slower.


The present invention provides a T cell receptor (TCR) having the property of binding to ALWGPDPAAA (derived from human pre-pro insulin (PPI) protein) HLA-A*02 complex and comprising a TCR alpha chain variable domain and a TCR beta chain variable domain. Also provided are nucleic acids encoding the TCR and cells engineered to present the TCR. Therapeutic agents based on TCRs of the invention can be used for the purpose of delivering immunosuppressive agents to beta cells in order to prevent their destruction by CD8^(+) T cells.


The invention provides a method for predicting whether a binding peptide, which binds to a target peptide presented by a Major Histocompatibility Complex (MHC) and is for administration to a subject, has the potential to cross react with another peptide in the subject in vivo. The method comprises the steps of identifying at least one binding motif in the target peptide to which the binding peptide binds; and searching for peptides that are present in the subject that comprise the at least one binding motif and that are not the target peptide. The presence of one or more such peptides indicates that the binding peptide has the potential to cross react in vivo.

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