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Transcriptional biomarkers and methods for detecting and isolating cancer cells in body fluids and tissue specimens

a transcriptional biomarker and cancer cell technology, applied in the field of detection and treatment of cancer, can solve the problems of increasing the cost of treatment, so as to extend the usefulness of the disclosed molecules and methods, and improve the effect of function

Inactive Publication Date: 2011-06-23
ONCOTX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides molecules that target cancer-specific transcriptional complexes (CSTCs) in melanoma cells. These molecules can be used for the treatment and detection of cancer, and can also be used to identify biomarkers for cancer diagnosis. The CSTCs are composed of different isoforms of cofactors and transcriptional co-regulators that are involved in malignant transformation. The invention also provides CSTC-targeting peptides and small molecules that can be used for inhibiting cancer cell proliferation, inhibiting tumor growth, detecting cancer, and inducing apoptosis. The CSTCs can be targeted using detectable molecules that specifically bind to them, indicating the presence of cancer.

Problems solved by technology

Cancer remains a significant health problem throughout the world.
Current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients.

Method used

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  • Transcriptional biomarkers and methods for detecting and isolating cancer cells in body fluids and tissue specimens
  • Transcriptional biomarkers and methods for detecting and isolating cancer cells in body fluids and tissue specimens
  • Transcriptional biomarkers and methods for detecting and isolating cancer cells in body fluids and tissue specimens

Examples

Experimental program
Comparison scheme
Effect test

example 1

Identification of Isoforms of Transcriptional Co-Regulators

[0123]This example demonstrates the results of an extensive in silico analysis of components of transcriptional co-regulators and use of PCR primers designed to identify novel iosforms with altered activity.

[0124]Material & Methods

[0125]Primary Tumors

[0126]Surgical specimens were obtained from human patients undergoing surgery for melanoma. Specimens were trypsinized and prepared for analysis using conventional techniques. RNA isolation was performed as described below.

[0127]Cell Culture

[0128]Human melanoma cell lines SK-MEL-28 and WM-266-4 were obtained from the American Type Culture Collection (ATCC; Manassas, Va.; SK-MEL-28 deposited by T. Takehashi and subject to release terms set by The Memorial Sloan-Kettering Cancer Center; WM-266-4 deposited by M. Herlyn). Cells were cultured according to recommendations of ATCC (DMEM, 10% FCS, penicillin+streptomycin) and used in experiments after two passages in the laboratory. Cel...

example 2

Effect of Interfering Peptides on Proliferation and Apoptosis of Melanoma Cells

[0140]Modeling of TFCs that contain isoforms of BAF57 and TRAP100 identified specific interactions that enabled us to synthesize small peptide libraries. Screening of these libraries using melanoma cell line SK-MEL-28 resulted in two peptides, denoted by us as BAF57 P12 and TRAP100 P05 that were found to stimulate apoptosis and inhibit growth of melanoma cells in vitro.

[0141]Amino acid sequences of SMARCE1 / BAF57 and TRAP100 isoforms. Unique, isoform specific sequences are underlined.

SMARCE1 / BAF57(SEQ ID NO: 10)MSKRPSYAPPPTPAPATQMPSTPGFVGYNPYSHLAYNNYRLGGNPGTNSRVTASSGITIPKPPKPPDKPLMPYMRYSRKVWDQVKASNPDLKLWEIGKIIGGMWRDLTDEEKQEYLNEYEAEKIEYNESMKAYHNSPAYLAYINAKSRAEAALEEESRQRQSRMEKGEPYMSIQPAEDPDDYDDGFSMKHTATARFQRNHRLISEILSESVVPDVRSVVTTARMQVLKRQVQSLMVHQRKLEAELLQIEERHQEKKRKFLESTDSFNNELKRLCGLKVEVDMEKIAAEIAQAEEQARKRQEEREKEAAEQAERSQSSIVPEEEQAANKGEEKKDDENIPMETEETHLEETTESQQNGEEGTSTPEDKESGQEGVDSMAEEGTSDSNTGSESNSATVEEPPTD...

example 3

Treatment of Human Melanoma Xenografts Using CSTC-Targeting Peptides

[0144]This example demonstrates the effect of therapeutic peptides on development of human melanomas in 4-week-old BALB / cOlaHsd-nu mice (Harlan, UK). Seven days after injection of melanoma cells, mice were randomly divided into 2 groups, 10 animals each. Control animals received intravenous (tail vein) injections of 50 microliters of phosphate buffer solution (PBS) every other day for 3 weeks. Test animals received intravenous (tail vein) injections of peptides BAF57 P12 and TRAP100 P05 (together) at a concentration of 0.5 mM each in 50 microliters of PBS every other day for 3 weeks. Last 2 injections were done using peptides labeled with fluorescein.

[0145]Therapeutic Peptides

BAF57 P12-PKKRKVRRRRRRRNDRLSDGDSKYSQTSHKLVQLLTRAP100 P05-PKKRKVRRRRRRRPQMQQNVFQYPGAGMVPQGEANFRed-NLS, blue-CPP and black-mimicking domains

[0146]One day following the last injection, animals were sacrificed and subcutaneous tumors were removed, ...

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Abstract

The invention provides molecules that target cancer-specific transcription complexes (CSTC), compositions and kits comprising CSTC-targeting molecules, and methods of using CSTC-targeting molecules for the treatment, detection and monitoring of cancer.

Description

[0001]This application is a continuation of application Ser. No. 11 / 777,271, filed Jul. 12, 2007, now U.S. Pat. No. ______, issued ______, 2011, which claims priority to U.S. provisional patent application No. 60 / 807,190, filed Jul. 12, 2006, the entire contents of each of which is incorporated herein by reference. Throughout this application various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention pertains.TECHNICAL FIELD OF THE INVENTION[0002]The present invention relates generally to detection and therapy of cancer. The invention is more specifically related to novel molecules directed against cancer-specific transcription complexes. The molecules of the invention can be used in vaccines and pharmaceutical compositions for the treatment of various cancers expressing the targeted transcription complexes, as we...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/53C07K14/47
CPCC07K14/4705A61K38/00A61P35/00
Inventor LIIK, ANZELIKAKAZANTSEVA, ANNA
Owner ONCOTX