Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Patent
1996-04-26
2000-05-09
Brusca, John S.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
424 91, 4241431, 435 6, 435 723, 435 78, 435 921, 514 44, 536 2431, 536 2433, A61K 4900, A61K 5100, C12Q 168, C01N 33566
Patent
active
060600373
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to compounds which comprise a receptor ligand moiety that binds to the ST receptor conjugated to a therapeutic or imaging moiety and to uses in the detection and treatment of colorectal tumors, particularly metastasized tumors. The present invention relates to compositions and kits for and methods of detecting metastasized colorectal tumor cells in samples, for determining whether or not a tumor is colorectal in origin, and for evaluating the extent of invasive activity of colorectal tumor cells in samples from the colon. This application is related to U.S. Ser. No. 08/141,892 filed Oct. 26, 1993 and U.S. Ser. No. 08/305,056 filed Sep. 13, 1994, the disclosures of both of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
Colorectal cancer is the third most common neoplasm worldwide. The mortality rate of newly diagnosed large bowel cancer approaches 50% and there has been little improvement over the past 40 years. Most of this mortality reflects local, regional and distant metastases.
Surgery is the mainstay of treatment for colorectal cancer but recurrence is frequent. Colorectal cancer has proven resistant to chemotherapy, although limited success has been achieved using a combination of 5-fluorouracil and levamisole. Surgery has had the largest impact on survival and, in some patients with limited disease, achieves a cure. However, surgery removes bulk tumor, leaving behind microscopic residual disease which ultimately results in recrudescence.
Early detection of primary, metastatic, and recurrent disease can significantly impact the prognosis of individuals suffering from colorectal cancer. Large bowel cancer diagnosed at an early stage has a significantly better outcome than that diagnosed at more advanced stages. Similarly, diagnosis of metastatic or recurrent disease earlier potentially carries with it a better prognosis.
Although current radiotherapeutic agents, chemotherapeutic agents and biological toxins are potent cytotoxins, they do not discriminate between normal and malignant cells, producing adverse effects and dose-limiting toxicities. Over the past decade, a novel approach has been employed to more specifically target agents to tumor cells, involving the conjugation of an active agent to molecules which binds preferentially to antigens that exist predominantly on tumor cells. These conjugates can be administered systemically and specifically bind to the targeted tumor cells. Theoretically, targeting permits uptake by cells of cytotoxic agents at concentrations which do not produce serious toxicities in normal tissues. Also, selective binding to targeted tumor cells facilitates detection of occult tumor and is therefore useful in designing imaging agents. Molecular targeting predominantly has employed monoclonal antibodies generated to antigens selectively expressed on tumor cells.
Immunoscintigraphy using monoclonal antibodies directed at tumor-specific markers has been employed to diagnose colorectal cancer. Monoclonal antibodies against carcinoembryonic antigen (CEA) labelled with .sup.99 Technetium identified 94% of patients with recurrent tumors. Similarly, .sup.111 Indium-labelled anti-CEA monoclonal antibodies successfully diagnosed 85% of patients with recurrent colorectal carcinoma who were not diagnosed by conventional techniques. .sup.125 Iodine-labelled antibodies have been effective in localizing more than 80% of the pathologically-confirmed recurrences by intraoperative gamma probe scanning.
Monoclonal antibodies have also been employed to target specific therapeutic agents in colorectal cancer. Preclinical studies demonstrated that anti-CEA antibodies labelled with .sup.90 Yttrium inhibited human colon carcinoma xenografts in nude mice. Antibodies generated to colorectal cancer cells and coupled to mitomycin C or neocarzinostatin demonstrated an anti-tumor effect on human colon cancer xenografts in nude mice and 3 patients with colon cancer.
Similar results in animals were obtained with monoclonal
REFERENCES:
patent: 4584268 (1986-04-01), Ceriani et al.
patent: 4683195 (1987-07-01), Mullis et al.
patent: 4683202 (1987-07-01), Mullis
patent: 4965188 (1990-10-01), Mullis et al.
patent: 5075216 (1991-12-01), Innis et al.
patent: 5160723 (1992-11-01), Welt et al.
patent: 5237015 (1993-08-01), Garbers et al.
patent: 5237051 (1993-08-01), Garbers et al.
patent: 5518888 (1996-05-01), Waldman
patent: 5601990 (1997-02-01), Waldman
patent: 5731159 (1998-03-01), Waldman
patent: 5879656 (1999-03-01), Waldman
Chelly, J. et al., "Illegitimate transcription: Transcription of any gene in any cell type", Proc. Natl. Acad. Sci. USA, 1989, 86, 2617-2621.
Chelly, J. et al., "Illegitimate Transcription: Application to the Analysis of Truncated Transcripts of the Dystrophin Gene in Nonmuscle Cultured Cells from Duchenne and Becker Patients", J. Clin. Invest., 1991, 88(4), 1161-1166.
Cooper, D.N. et al., "Ectopic (Illegitimate) Transcription: New Possibilities for the Analysis and Diagnosis of Human Genetic Disease", Ann. Med., 1994, 26(1), 9-14.
Kaplan, J.C. et al., "Illegitimate transcription: its use in the study of inherited disease", Human Mutation, 1992, 1(5), 357-360 (Abstract only).
Negrier, C. et al., "Illegitimate transcription: its use for studying genetic abnormalities in lymphoblastoid cells from patients with Glanzmann thrombasthenia", British J. Haematology, 1998, 100(1), 33-39.
Zippelius, A. et al., "Limitations of Reverse-Transcriptase Polymerase Chain Reaction Analyses for Detection of Micrometastatic Epithelial Cancer Cells in Bone Marrow", J. Clin. Oncology, 1997, 15(7), 2701-2708.
Aitken, R. et al., "Recombinant enterotoxins as vaccines against Escherichia coli-mediated diarrhoea", Vaccine, 1993, 11(2), 227-233.
Field, M., "Role of Cyclic Nucleotides in Enterotoxic Diarrhea", Mol. Cyclic Nucl. Res., 1980, 12, 267-277.
Giannella, R.A., "Pathogenesis of Acute Bacterial Diarrheal Disorders", Ann. Rev. Med., 1981, 32, 341-357.
Rao, M.C. et al., "Enterotoxins and Anti-toxins: Enterotoxins and ion transport", Biochem., 1984, 12, 177-180.
Almenoff et al., "Ligand-based Histochemical Localization and Capture of Cells Expressing Heat-Stable Enterotoxin Receptors", Molecular Microbiology 8: 865-873 (1993).
Bjorn et al., "Antibody-Pseudomonas Exotoxin A Conjugates Cytotoxic to Human Breast Cancer Cells In Vitro", Cancer Research 46: 3262-3267 (1986).
Bjorn et al., "Evaluation of Monoclonal Antibodies for the Development of Breast Cancer Immunotoxins", Cancer Research 45: 1214-1221 (1985).
Bodansky et al., "Peptide Synthesis", John Wiley and Sons, 2d Ed. (1976).
Burgess et al., "Biological Evaluation of a Methanol-Soluble, Heat-Stable Escherichia coli Enterotoxin in Infant Mice, Pigs, Rabbits, and Calves", Infection and Immunity 21: 526-531 (1978).
Cawley and Herschman, "Epidermal Growth Factor-Toxin A Chain Conjugates: EGF-Ricin A is a Potent Toxin While EGF-Diphtheria Fragment A is Nontoxic", Cell 22: 563-570 (1980).
Ceriani, R. et al., "Variability in Surface Antigen Expression of Human Breast Epithelial Cells Cultured from Normal Breast, Normal Tissue Peripheral to Breast Carcinomas, and Breast Carcinomas", Cancer Res. Jul. 1984, 44, 3033-3039.
Ceriani, R. et al., "Circulating Human Mammary Epithelial Antigens in Breast Cancer", PNAS USA 1982, 79, 5420-5424.
Chan and Giannella, "Amino Acid Sequence of Heat-stable Enterotoxin Produced by Escherichia coli Pathogenic for Man", J. Biol. Chem. 256: 7744-7746 (1981).
Chung and Collier, "Enzymatically Active Peptide from the Adenosine Diphosphate-Ribosylating Toxin of pseudomonas Aeruginosa" Infection and Immunity 16: 832-841 (1977).
Cohen, M. et al., "Receptors for Escherichia coli Heat Stable Enterotoxin in Human Intestine and in a Human Intestinal Cell Line (Caco-2)", J. Of Cellular Physiol. 1993, 156, 138-144.
Corstens, F. And van der Meer, Jos. W.M., "Chemotactic Peptides: New Locomotion for Imaging of Infection?", J. Nucl. Med. 1991, 32(3), 491-494.
Cumber et al., "Preparation of Antibody-Toxin Conjugates", Me
Brusca John S.
Larson Thomas G.
Thomas Jefferson University
LandOfFree
Compositions that specifically bind to colorectal cancer cells a does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions that specifically bind to colorectal cancer cells a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions that specifically bind to colorectal cancer cells a will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1061820