Multivalent T cell receptor complexes
OwnerBent Karsten Jakobsen, Jonathan Michael Boulterinventors
Life of this patent
Estimating the term…
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.
Claims33
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.
The TCR complex according to any preceding claim, wherein the T cell receptors are in the form of multimers of two or more T cell receptors.
The TCR complex according to any preceding claim, wherein the T cell receptors are associated with one another via a linker molecule.
The TCR complex according to any preceding claim, comprising a multimerised recombinant T cell receptor heterodimer having enhanced binding capability compared to a non-multimeric T cell receptor heterodimer.
A multivalent TCR complex comprising a multimerised recombinant T cell receptor heterodimer having enhanced binding capability compared to a non-multimeric T cell receptor heterodimer.
The TCR complex according to any preceding claim, wherein the T cell receptor is a refolded recombinant T cell receptor which comprises:
- i) a recombinant T cell receptor (α or γ chain extracellular domain having a first heterologous C-terminal dimerisation peptide;
- and
- ii) a recombinant T cell receptor β or δ chain extracellular domain having a second C-terminal dimerisation peptide which is specifically heterodimerised with the first dimerisation peptide to form a heterodimerisation domain.
The TCR complex according to any preceding claim, wherein the T cell receptors are associated with a lipid bilayer.
The TCR complex according to any preceding claim, further comprising a detectable label.
The TCR complex according to any preceding claim, further comprising a therapeutic agent such as a cytotoxic agent or an immunostimulating agent.
The TCR complex according to any preceding claim, in a pharmaceutically acceptable formulation for use in vivo.
A method for detecting MHC-peptide complexes which method comprises:
- (i) providing (a) a synthetic multivalent T cell receptor complex comprising a plurality of T cell receptors, and/or (b) a synthetic multivalent T cell receptor complex comprising a multimerised recombinant T cell receptor heterodimer having enhanced binding capability compared to a non-multimeric T cell receptor heterodimer, said T cell receptors being specific for the MHC-peptide complexes;
- (ii) contacting the multivalent TCR complex with the MHC-peptide complexes;
- and
- (iii) detecting binding of the multivalent TCR complex to the MHC-peptide complexes.
A method for delivering a therapeutic agent to a target cell, which method comprises:
- (i) providing (a) a synthetic multivalent TCR complex comprising a plurality of T cell receptors, and/or (b) a synthetic multivalent TCR complex comprising a multimerised recombinant T cell receptor heterodimer having enhanced binding capability compared to a non-multimeric T cell receptor heterodimer, said T cell receptors being specific for the MHC-peptide complexes and the multivalent TCR complex having the therapeutic agent associated therewith;
- (ii) contacting the multivalent TCR complex with potential target cells under conditions to allow attachment of the T cell receptors to the target cell.
Dependencies are inferred from the claim text.