Compositions and methods for the treatment of tumors
AssigneeGenentech, Inc.
InventorsSarah C. Bodary, Karen L. Fisher
Life of this patent
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Abstract
The invention concerns compositions and methods for the diagnosis and treatment of neoplastic cell growth and proliferation in mammals, including humans. The invention is based upon the identification of an ADAM8 gene that is amplified in the genome of tumor cells. Such gene amplification is associated with the overexpression of the gene product as compared to normal cells of the same tissue type and contributes to tumorigenesis. Accordingly, the ADAM8 protein encoded by the amplified gene is a useful target for the diagnosis and/or treatment (including prevention) of certain cancers, and acts as a predictor of the prognosis of tumor treatment.
Claims47
An isolated antibody that binds to an ADAM8 polypeptide.
An antagonist of an ADAM8 polypeptide.
An isolated nucleic acid molecule that hybridizes to the complement of a nucleic acid sequence that encodes an ADAM8 polypeptide.
A method for determining the presence of an ADAM8 polypeptide in a sample suspected of containing said polypeptide, said method comprising exposing the sample to an anti-ADAM8 antibody and determining binding of said antibody to an ADAM8 polypeptide in said sample.
A method of diagnosing a tumor in a mammal, said method comprising detecting the level of expression of a gene encoding an ADAM8 polypeptide (a) in a test sample of tissue cells obtained from the mammal, and (b) in a control sample of known normal tissue cells of the same cell type, wherein a higher expression level in the test sample is indicative of the presence of tumor in the mammal from which the test tissue cells were obtained.
A method of diagnosing a tumor in a mammal, said method comprising (a) contacting an anti-ADAM8 antibody with a test sample of tissue cells obtained from the mammal, and (b) detecting the formation of a complex between the anti-ADAM8 antibody and an ADAM8 polypeptide in the test sample, wherein the formation of a complex is indicative of the presence of a tumor in said mammal.
A cancer diagnostic kit comprising an anti-ADAM8 antibody and a carrier in suitable packaging.
A method for inhibiting the growth of tumor cells, said method comprising exposing tumor cells that express an ADAM8 polypeptide to an effective amount of an agent that inhibits an activity of an ADAM8 polypeptide, wherein growth of said tumor cells is inhibited.
A method for inhibiting the growth of tumor cells, said method comprising exposing tumor cells that express an ADAM8 polypeptide to an effective amount of an agent that inhibits the expression of an ADAM8 polypeptide, wherein growth of said tumor cells is thereby inhibited.
An article of manufacture, comprising:
- a container;
- a label on the container;
- and
- a composition comprising an active agent contained within the container, wherein the composition is effective for inhibiting the growth of tumor cells and wherein the label on the container indicates that the composition is effective for treating conditions characterized by overexpression of an ADAM8 polypeptide in said tumor cells as compared to in normal cells of the same tissue type.
A method of identifying a compound that inhibits an activity of an ADAM8 polypeptide, said method comprising contacting a candidate compound with an ADAM8 polypeptide under conditions and for a time sufficient to allow the two components to interact and determining whether an activity of said ADAM8 polypeptide is inhibited.
A method of identifying a compound that inhibits an activity of an ADAM8 polypeptide, said method comprising the steps of (a) contacting cells and a candidate compound to be screened in the presence of an ADAM8 polypeptide under conditions suitable for the induction of a cellular response normally induced by an ADAM8 polypeptide and (b) determining the induction of said cellular response to determine if the test compound is an effective antagonist.
A method for identifying a compound that inhibits the expression of an ADAM8 polypeptide in cells that express said polypeptide, wherein said method comprises contacting said cells with a candidate compound and determining whether expression of said ADAM8 polypeptide is inhibited.
Dependencies are inferred from the claim text.