Compositions and methods for inhibiting metastasis
First Claim
1. A composition for use in inhibiting metastasis comprising:
- a) a CD26 antagonist, plasminogen antagonist, ADA antagonist and/or angiostatin allosteric promoter, and b) a suitable carrier.
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Accused Products
Abstract
Compounds, compositions and methods for inhibiting metastasis, and screening methods for identifying compounds are disclosed. The compounds bind to CD26 and/or plasminogen, and when so bound, inhibit the Ca+2 signaling cascade that results in the formation of MMP-9. When the compounds directly bind to CD26 in a manner that inhibits the signaling cascade, they inhibit metastasis. When the compounds enhance the ability of angiostatin to bind to CD26 and inhibit the signaling cascade, they are angiostatin allosteric promoters. The compounds can also bind to CD26 in a manner which inhibits the binding of ADA to CD26/DPP IV, and such compounds used in methods for inhibiting deamination of adenosine. The compounds can be, for example, antibodies, antibody fragments, enzymes, peptides, nucleic acids such as oligonucleotides, or small molecules. The antibodies can be monoclonal, humanized, or polyclonal antibodies. The compounds can be conjugated to or combined with various cytotoxic agents and/or labeled compounds. Methods for inhibiting tumor metastasis can be used to treat patients suffering from such tumors.
14 Citations
33 Claims
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1. A composition for use in inhibiting metastasis comprising:
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a) a CD26 antagonist, plasminogen antagonist, ADA antagonist and/or angiostatin allosteric promoter, and b) a suitable carrier. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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- 10. A method of inhibiting tumor metastasis, comprising administering to a patient in need of treatment thereof an effective, metastasis inhibiting amount of a CD26 antagonist, plasminogen antagonist, ADA antagonist and/or angiostatin allosteric promoter.
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19. A method of screening a test compound for its ability to inhibit metastasis comprising:
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i) contacting the test compound with CD26 under conditions such that angiostatin would bind to the CD26 in the absence of the test compound, and ii) determining the binding affinity of the compound to CD26. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27)
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28. A method of screening a test compound for its ability to inhibit metastasis comprising:
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i) contacting the test compound with a cell that expresses CD26 under conditions such that angiostatin would bind to the CD26 in the absence of the test compound and under conditions such that the Ca+2 signaling cascade that results in formation of MMP-9 would otherwise occur, ii) determining the amount of MMP-9 formed after the compound is contacted with the CD26, and iii) comparing the amount of MMP-9 formed with a baseline amount of MMP-9 formed when no test compound is added. - View Dependent Claims (29)
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30. A monoclonal antibody or antibody fragment thereof specific for CD26 that functions as an CD26 antagonist.
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31. A monoclonal antibody or antibody fragment thereof that functions as an angiostatin allosteric promoter.
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32. A monoclonal antibody or antibody fragment thereof that functions as a plasminogen antagonist.
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33. A monoclonal antibody or antibody fragment thereof that functions as an ADA antagonist.
Specification