Assays for O.sup.6 -methylguanine-DNA methyltransferase

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

435 721, 435 792, 435 795, 435 7021, 43524027, 435960, 435193, 53038826, C12Q 100, C12N 520, C07K 1528, G01N 33533

Patent

active

054078040

ABSTRACT:
Assays for the DNA repair protein O.sup.6 -methylguanine-DNA methyltransferase (MGMT) are provided which employ monoclonal antibodies prepared using MGMT having transferase activity, as opposed to denatured MGMT or MGMT fragments. The monoclonal antibodies are able to recognize MGMT in single cell preparations (immunohistochemical staining assays) and in cell extracts (immunoassays). In connection with immunohistochemical staining, the use of a fluorescent readout coupled with digitization of the cell image allows for quantitative measures of MGMT levels in, for example, tumor biopsy samples. Such quantitative measures can be used to determine which patients are likely to benefit from chemotherapy using alkylating agents since tumor cells having low MGMT levels are more likely to be killed by such agents than those with high MGMT levels.

REFERENCES:
patent: 5077211 (1991-12-01), Yarosh
patent: 5272079 (1993-12-01), Yarosh
patent: 5296231 (1994-03-01), Yarosh
Herlow et al (1988) Antibodies: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, N.Y., pp. 72-77, 92-97, 128-135 & 141-157.
Goding (1983) "Monoclonel Antibodies: Principles and Practice", Academic Press, Orlando, pp. 56-91, 212-218 & 234-239.
Inoue (1986) "Video Microscopy" Plenum Press, New York, pp. 327-403 and 415-416.
Ayi, et al., "Interacellular Localization of Human DNA Repair Enzyme Methylguanine-DNA Methyltransferase by Antibodies and Its Importance," Cancer Research, 1992, 52:6423-6430.
Lee, et al., "Immunohistological examination of the inter- and intracellular distribution of O.sup.6 -alkylguanine DNA-alkyltransferase in human liver and melanoma," Br. J. Cancer, 1992, 66:355-360.
Lee, et al., "Expression of O.sup.6 -Alkylguanine-DNA-Alkyltransferase in situ in Ovarian and Hodgkin's Tumours," Eur. J. Cancer, 1993, 9:1306-1312.
Rafferty, et al., "Isolation and partial characterisation of a Chinese hamster O.sup.6 -alkylguanine DNA alkyltransferase cDNA", Nucleic Acids Research, 1992, 20:1891-1895.
Wu, et al., "Expression of Human O.sup.6 -Methylguanine-DNA Methyltransferase in Chinese Hamster Ovary Cells and Restoration of Cellular Resistance to Certain N-Nitroso Compounds," Molecular Carcinogenesis, 1991, 4:482-488.
Yarosh, D., "The Role of O.sup.6 -Methylguanine-DNA Methyltransferase in Cell Survival, Mutagenesis and Carcinogenesis", Mutation Reseach, vol. 145, pp. 1-16, 1985.
Pegg, A. E., "Properties of Mammalian O.sup.6 -Alkylguanine-DNA Alkyltransferase", Mutation Research, vol. 233, pp. 165-175, 1990.
Pegg, A. E., "Mammalian O.sup.6 -Alkylguanine-DNA Alkyltransferase: Regulation and Importance in Response to Alkylating, Carcinogenic and Therapeutic Agents", Cancer Research, vol. 50, pp. 6119-6129, 1990.
Watatani, W., et al., "Analysis of N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG)-Induced DNA Damage in Tumor Cell Strains from Japanese Patients and Demonstration of MNNG Hypersensitivity of MER.sup.- Xenografts in Athymic Nude Mice", Carcinogenesis, vol. 6, pp. 549-553, 1985.
Aida, T., et al., "Inhibition of O.sup.6 -Alkylguanine-DNA Alkyltransferase Activity Potentiates Cytotoxicity and Induction of SCEs in Human Glioma Cells Resistant to 1,3-Bis(2-Chloroethyl)-1-Nitrosourea", Carcinogenesis, vol. 8, pp. 1219-1223, 1987.
Fujio, C., et al., "Hypersensitivity of Human Tumor Xenografts Lacking O.sup.6 -Alkylguanine-DNA Alkyltransferase to the Anti-Tumor Agent 1-(4-Amino-2-Methyl-5-Pyrimidinyl) Methyl-3-(2-Chloroethyl)-3-Nitrosourea", Carcinogenesis, vol. 10, pp. 351-356, 1989.
Brent, T., "Isolation and Purification of O.sup.6 -Alkylguinanine-DNA Alkyltransferase from Human Leukemic Cells. Prevention of Chloroethylnitrosourea-Induced Cross-Links by Purified Enzyme", Pharmacological Therapeutics, vol. 31, pp. 121-139, 1985.
Von Wronski, M., et al., "Monoclonal Antibodies Against Human O.sup.6 -Alkylguanine-DNA Alkyltransferase", Abstract in Proceedings of the American Association for Cancer Research, vol. 30, pp. 486, 1989.
Brent, T., et al., "Immunoaffinity Purification of Human O.sup.6 -Methylguanine-DNA Methyltransferase Using Newly Developed Monoclonal Antibodies", Cancer Research, vol. 50, pp. 58-61, 1990.
Von Wronski, M., et al., "Expression of O.sup.6 -Alkylguanine-DNA Alkyltransferase in MER.sup.+ and MER.sup.- Human Cell Extracts Probed with Specific Monoclonal Antibodies", Cancer Communications, vol. 1, pp. 323-327, 1989.
Yarosh, D., et al., "Monoclonal Antibodies Against the Human O.sup.6 -Methylguanine-DNA Methyltransferase", Abstract in Proceedings of the American Association for Cancer Research, vol. 29, p. 1, 1988.
Ostrowski, L., et al., "Production and Characterization of Antipeptide Antibodies Against Human O.sup.6 -Methylguanine-DNA Methyltransferase", Cancer Research, vol. 51, pp. 3339-3344, 1991.
Pegg, A. E., et al., "Production of Antibodies to Peptide Sequences Present in Human O.sup.6 -Alkylguanine-DNA Alkyltransferase and Their Use to Detect this Protein in Cell Extracts", Carcinogenesis, vol. 12, No. 9, pp. 1671-1677, 1991.
Pegg, A. E., et al., "Use of Antibodies to Human O.sup.6 -Alkylguanine-DNA Alkyltransferase to Study the Content of this Protein in Cells Treated with O.sup.6 -Benzylguanine or N-Methyl-N'-Nitro-N-Nitrosoguanidine", Carcinogenesis, vol. 12, No. 9, pp. 1679-1683, 1991.
Lee, S. M., et al., "Regional and Cellular Heterogeneity of Expression of O.sup.6 -Alkylguanine-DNA Alkyltransferase in Melanoma", Abstract in Proceedings of the American Association for Cancer Research, vol. 33, Mar. 1992, p. 547.
Pegg, A. E., et al., "Repair of DNA Containing O.sup.6 -Alkylguanine", Federation of American Societies of Experimental Biology Journal, vol. 6, Mar. 1992, pp. 2302-2310.
Campbell, A. M., Monoclonal Antibody Technology: The Production and Characterization of Rodent and Human Hybridomas, Elsevier, N.Y., 1984, pp. 88-89.
Goding, J. W., Monoclonal Antibodies: Principles and Practice, Harcourt Brace Jovanovich, New York, 1986, pp. 28-31.
Tano, K., et al., "Isolation and Structural Characterization of a cDNA Clone Encoding the Human DNA Repair Protein for O.sup.6 -Alkylguanine", Proc. Natl. Acad. Sci. USA, vol. 87, pp. 686-690, 1990.
Hayakawa, H., et al., "Expression and Cloning of Complementary DNA for a Human Enzyme that Repair O.sup.6 -Methylguanine in DNA", J. Mol. Biol., vol. 213, pp. 739-747, 1991.
Rydberg, B., et al., "cDNA Cloning and Chromosomal Assignment of the Human O.sup.6 -Methylguanine-DNA Methyltransferase", J. Biol. Chem., vol. 265, pp. 9563-9569, 1990.
Von Wronski, M. A., et al., "Structural and Immunological Comparison of Indigenous Human O.sup.6 -Methylguanine-DNA Methyltransferase with that Encoded by a Cloned cDNA", J. Biol. Chem., vol. 266, pp. 1064-1070, 1991.
Shiota, S., et al., "Characterization of cDNA Encoding Mouse DNA Repair Protein O.sup.6 -Methylguanine-DNA Methyltransferase and High-Level Expression of the Wild-Type and Mutant Proteins in Escherichia coli.," Biochemistry 31:1897-1903, 1992.
Sakumi, N., et al., "Cloning and Expression of cDNA for Rat O.sup.6 -Methylguanine-DNA Methyltransferase," Nucleic Acids Research, 19:5597-5601, 1991.
Rydberg, B., et al., "Active Site Amino Acid Sequence of the Bovine O.sup.6 -Methylguanine-DNA Methyltransferase", Nucleic Acids Res., vol. 18, pp. 17-21, 1990.
Kohler, et al., Nature, vol. 256, pp. 495-497, 1975.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Assays for O.sup.6 -methylguanine-DNA methyltransferase does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Assays for O.sup.6 -methylguanine-DNA methyltransferase, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Assays for O.sup.6 -methylguanine-DNA methyltransferase will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-66166

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.