Multivalent T cell receptor complexes
AssigneeAvidex Limited
InventorsBent Jakobsen, Jonathan Boulter
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Abstract
The present invention relates to a synthetic multivalent T cell receptor complex for binding to a MHC-peptide complex, which multivalent T cell receptor complex comprises a plurality of T cell receptors specific for the MHC-peptide complex. It is preferred that the T cell receptors are refolded recombinant soluble T cell receptors. The synthetic multivalent T cell receptor complex can be used for delivering therapeutic agents or for detecting MHC-peptide complexes, and methods for such uses are also provided.
Claims20
A synthetic multivalent T cell receptor (TCR) complex for binding to a MHC-peptide complex, which TCR complex comprises a plurality of T cell receptors specific for the MHC-peptide complex, wherein each TCR in the complex is a refolded recombinant TCR which comprises:
- i.) a recombinant TCR α or γ chain extracellular domain having a first C-terminal dimerization peptide which is heterologous to the α or γ chain;
- and
- ii.) a recombinant TCR β or δ chain extracellular domain having a second C-terminal dimerization peptide which is heterologous to the β or δ chain and which is specifically heterodimerized with the first heterodimerization peptide to form a heterodimerization domain,
- wherein a disulfide bond present in native TCRs between the α and β or γ and δ chains adjacent to the cytoplasmic domain is absent from the recombinant TCR.
A multivalent TCR complex comprising a multimerized recombinant T cell receptor heterodimer having enhanced binding capability compared to a non-multimeric T cell receptor heterodimer, wherein each TCR in the complex is a refolded recombinant TCR which comprises:
- i) a recombinant TCR α or γ chain extracellular domain having a first C-terminal dimerization peptide which is heterologous to the α or γ chain;
- and
- ii) a recombinant TCR β or δ chain extracellular domain having a second C-terminal dimerization peptide which is heterologous to the β or δ chain and which is specifically heterodimerized with the first dimerization peptide to form a heterodimerization domain,
- wherein a disulfide bond present in native TCRs between the α and β or γ and δ chains adjacent to the cytoplasmic domain, is absent from the recombinant TCR.
Dependencies are inferred from the claim text.