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OwnerMartin Lackmann, Sabine Wimmer-Kleikamp +3inventors
InventorsMartin Lackmann, Sabine Wimmer-Kleikamp, Andrew Scott, Christopher Vearing, Andrew Boyd
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Methods and compositions for modulating ephrin/Eph receptor-mediated cell adhesion and/or cell repulsion are provided, particularly in relation to preventing, inhibiting or delaying tumour cell metastasis through modulation of Eph receptor-ephrin binding interactions and subsequent Eph receptor signalling. Particular agents useful according to the invention are agents which interfere with a ephrin-Eph receptor binding such as soluble ephrins and Eph receptors and antibodies directed to ephrins and Eph receptors, ephrin-cytotoxic drug conjugates which kill tumour cells, metalloprotease inhibitors and inhibitors of protein tyrosine phosphatase activity.
A method of modulating cell adhesion and/or cell repulsion, said method including the step of administering an agent for modulating the ability of a cell expressing an Eph receptor to respond to ephrin binding, whereby the ability of said one cell to adhere to another cell is either facilitated or inhibited or cell-contact repulsion between said cell and said another cell is either enhanced or reduced.
A method of preventing, inhibiting or delaying tumour metastasis in a mammal including the step of administering to said mammal an agent that modulates the ability of an Eph receptor expressed by a tumour cell to bind, proteolytically cleave, internalize or otherwise respond to an ephrin expressed by another cell, whereby adhesion between said tumour cell and said another cell is reduced or inhibited.
A pharmaceutical composition that comprises and agent for use in modulating Eph receptor-ephrin mediated cell adhesion and/or cell repulsion, together with a pharmaceutically-acceptable carrier diluent or excipient.
(canceled)
The method of claim 77, wherein the agent is an inhibitor of a protein tyrosine phosphatase SP-2, LMWPTP or a related protein tyrosine phosphatase.
The method of claim 77, wherein the agent is a metalloprotease inhibitor.
The method of claim 77, wherein the agent is a hydrolysable soluble ephrin-A5 conjugated cytotoxic drug, which upon Eph-receptor-mediated internalisation, causes cell de-adhesion and/or repulsion.
The method of claim 77, wherein the agent is an inhibitor of a protein tyrosine phosphatase SHP-2, LMWPTP or a related protein tyrosine phosphatase.
The method of claim 77, wherein the agent comprises a soluble ephrin or Eph receptor-binding domain thereof.
The method of claim 77, wherein the agent comprises a soluble Eph receptor or ligand-binding domain thereof.
The method of claim 77, wherein the agent comprises an antibody directed to an ephrin or Eph-receptor binding domain thereof.
The method of claim 77, wherein the agent comprises an antibody directed to an ephrin or Eph receptor binding domain thereof.
The method of claim 77, wherein the agent is an antibody directed to an ephrin-interaction or binding domain of an Eph receptor.
A method of identifying an agent that modulates cell adhesion and/or cell repulsion, said method including the step of determining whether said agent modulates cell adhesion or cell repulsion which normally occurs in response to Eph receptor/ephrin binding.
A method of preventing, inhibiting or delaying tumour cell metastasis, said method comprising administering to a mammal in need thereof an agent that modulates Eph receptor-ephrin mediated cell adhesion and/or cell repulsion.
Dependencies are inferred from the claim text.