Other

Oxford Biomedica (uk) Limited

Institute of Virology of the Slovak Academy of Sciences

Bayer Healthcare LLC

Institute of Virology

Adrian Llewllyn Harris

Peter John Ratcliffe

Christopher William Pugh

John David Firth

Ian James Stratford

Michael W DeGregorio

Julian M Marshall

Claire Elizabeth Lewis

Stanley Liu

Lauri V Kangas

Ruth Muschel

Peter J Ratcliffe

The disclosure provides methods of treating cancer, tumors, and neoplasias by administering ionizing radiation and an anti-DLL4 antibody or a DLL4-binding fragment.

Methods of enhancing the response to radiation in tumor therapy using anti-DLL4 antibodies

Identified herein is the location of the MN protein binding site, and MN proteins/polypeptides that compete for attachment to vertebrate cells with immobilized MN protein. Such MN proteins/polypeptides prevent cell-cell adhesion and the formation of intercellular contacts. The MN protein binding site is a therapeutic target that can be blocked by organic or inorganic molecules, preferably organic molecules, more preferably proteins/polypeptides that specifically bind to that site. Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Vectors are provided that encode the variable domains of MN-specific antibodies and a flexible linker polypeptide separating those domains. Further vectors are disclosed that encode a cytotoxic protein/polypeptide operatively linked to the MN gene promoter or a MN gene promoter fragment comprising the HIF-1 consensus binding sequence, and which vectors preferably further encode a cytokine. The MN gene promoter is characterized, and the binding site for a repressor of MN transcription is disclosed. Further, the hypoxia inducibility of the MN gene and the uses of such inducibility are disclosed.

MN gene and protein

Herein disclosed are methods that are predictive of resistance to endocrine therapy in an estrogen receptor-positive (ER-positive) breast cancer patient. An exemplary method comprises detecting the overexpression of MN/CA9 gene expression product(s) in a sample from an affected subject, wherein if MN/CA9 is overexpressed, then the subject is considered to have a greater probability of resistance to endocrine therapy, particularly tamoxifen, and a corresponding poorer prognosis if undergoing endocrine therapy, than if MN/CA9 is not overexpressed. MN/CA9 gene expression products useful in the predictive/prognostic methods include MN/CA IX, MN proteins/polypeptides, MN nucleic acids and soluble MN/CA IX antigen (s-CA IX). The methods are useful as an aid in the selection of treatment for a patient with an ER-positive breast tumor. The methods of the invention can be used, for example, to identify those patients requiring additional/alternative therapies, preferably, but not necessarily, therapies that are not affected by acidic pH. The methods also comprise the use of diagnostic/prognostic imaging to detect MN/CA IX in a patient tumor, wherein the presence of MN/CA IX in one or more tumors is indicative of probable resistance to antiestrogen therapy, particularly to tamoxifen.

MN/CA IX and breast cancer therapy

The invention relates to the exploitation of the migratory behavior of mononuclear phagocytes with a view to targeting therapeutic drug delivery. The invention therefore concerns the attachment or incorporation of a therapeutic agent to or into a mononuclear phagocyte and the subsequent migration of the munonuclear phagocyte to a target area.

Mononuclear phagocytes in therapeutic drug delivery

Nucleic acid constructs comprising hypoxia response elements in operable linkage with a coding sequence of a gene of interest, and methods for expressing a nucleic acid sequence using the constructs, are disclosed. In particular, such nucleic acid constructs comprise genes encoding prodrug activation systems or cytokines.

Methods for expressing nucleic acid sequences using nucleic acid constructs comprising hypoxia response elements

Nucleic acid constructs comprising hypoxia response elements

This invention relates to the use of a compound comprising toremifene or its metabolites N-demethyltoremifene or 4-hydroxytoremifene or its non-toxic pharmaceutically acceptable salts for the reversal of multidrug resistance of cancer cells to cytotoxic drugs in the treatment of cancer with such cytotoxic drugs.

Use of toremifene and its metabolites for the reversal of multidrug

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Oxford, United Kingdom

Adrian Llewllyn Harris