Compositions and methods for the therapy and diagnosis of breast cancer

A composition and breast tumor technology, applied in chemical instruments and methods, translation products of oncogenes, biochemical equipment and methods, etc.

Inactive Publication Date: 2005-07-27
CORIXA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, application of established markers often leads to uninterpretable results, and the high mortality rate among breast cancer patients shows the need for improvement in the treatment, diagnosis and prevention of this disease

Method used

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  • Compositions and methods for the therapy and diagnosis of breast cancer
  • Compositions and methods for the therapy and diagnosis of breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0831] Isolation and Characterization of Breast Tumor Peptides

[0832] This example describes the isolation of breast tumor polypeptides from a breast tumor cDNA library.

[0833] A cDNA subtraction library comprising breast tumor cDNA subtracted from normal breast cDNA was constructed as follows. Total RNA was extracted from primary tissues using Trizol reagent (Gibco BRL LifeTechnologies, Gaithersburg, MD) as described by the manufacturer. PolyA+ RNA was purified using oligo-dT-cellulose columns according to standard protocols. First-strand cDNA was synthesized using primers provided by the Clontech PCR-screen cDNA subtraction kit (Clotech, Palo Alto, CA). The driver DNA (driver DNA) contained cDNA from two normal breast tissues and the tester cDNA (tester cDNA) was from three primary breast tumors. Double strands of tester and driver cDNA were synthesized and digested with a combination of endonucleases recognizing six base pair DNA (MLuI, MscI, PvuII, SalI and...

Embodiment 2

[0850] Isolation and Characterization of Breast Tumor Polypeptides Obtained by PCR-Based Subtraction Using SCID-Passaged Tumor RNA

[0851] Human mammary tumor antigens were obtained by PCR-based subtraction using mammary tumor RNA passaged from SCID mice as follows. SCID mice were implanted with human breast tumors and harvested at passage 5 or 6 as described in Patent Application Serial No. 08 / 556,659, U.S. Patent No. 5,986,170, filed 11 / 12 / 95. Differentially expressed genes found between early and late SCID passaged tumors may be stage-specific and thus useful in therapeutic and diagnostic applications. Total RNA was prepared from the first and sixth passages of snap-frozen SCID-passaged human breast tumors.

[0852]PCR-based subtraction was performed essentially as described above. In the first subtraction (called T9), RNA from first-generation tumors is subtracted from RNA from sixth-generation tumors to identify more aggressive, later-generation-specific antigens. Of ...

Embodiment 3

[0857] synthetic peptide

[0858] Peptides can be synthesized on a Perkin Elemer / Applied Biosystems Division 430A peptide synthesizer using FMOC chemistry with HPTU (O-benzotriazole-N,N,N',N',-tetramethyluronium hexafluorophosphate) activation. A Gly-Cys-Gly sequence can be attached to the amino terminus of the peptide to provide a method for conjugation, attachment to immobilized surfaces or labeling of the peptide. Peptides can be cleaved from the solid support using the following cleavage mixture: trifluoroacetic acid: ethanedithiol: thioanisole: water: phenol (40:1:2:2:3). After two hours of cleavage, the peptide can be precipitated in cold methyl-tert-butyl ether. The peptide pellet can then be dissolved in water containing 0.1% trifluoroacetic acid (TFA) and lyophilized before purification by C18 reverse phase HPLC. Peptides can be eluted with a gradient of 0%-60% acetonitrile (with 0.1% TFA) in water (with 0.1% TFA). Following freezing of purifie...

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Abstract

Compositions and methods for treating and diagnosing cancer, such as breast cancer, are disclosed. Compositions may include one or more breast tumor proteins, immunogenic portions thereof, or polynucleotides encoding such portions. Alternatively, the therapeutic composition may include antigen presenting cells expressing a breast tumor protein or T cells specific for cells expressing such protein. Such compositions can be used, for example, in the prevention and treatment of diseases such as breast cancer. Also provided are diagnostic methods based on the detection of breast tumor proteins or mRNA encoding such proteins in a sample.

Description

field of invention [0001] The present invention relates generally to the treatment and diagnosis of cancers such as breast cancer. The invention more particularly relates to polypeptides comprising at least part of mammary tumor proteins and polynucleotides encoding these polypeptides. These polypeptides and polynucleotides can be used in compositions for preventing and treating breast cancer as well as diagnosing and monitoring these cancers. Background of the invention [0002] Breast cancer is an important health problem for women in the United States and around the world. Despite advances in detection and treatment of the disease, breast cancer remains the second leading cause of cancer-related death in women, affecting more than 180,000 women in the United States each year. For North American women, the lifetime risk of developing breast cancer is one in eight. [0003] There are currently no vaccines or other generally successful methods to prevent and treat breast ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47A61K48/00C12N15/62A61K38/37G01N33/68C12N15/86C12N5/10C12N15/09A61K35/12A61K35/14A61K38/00A61K39/00A61K39/395A61P35/00A61P43/00C07K7/00C07K14/82C07K16/32C07K19/00C12N1/15C12N1/19C12N1/21C12N5/07C12N5/0783C12N5/09C12N9/00C12Q1/68
CPCA61K2039/57C07K2319/00C07K14/4748C12N9/00Y10S977/924A61K35/12C12Q1/6886A61K2039/5154A61K38/00C07K2319/003A61K39/00C07K14/47C12Q2600/158A61P35/00A61P43/00
Inventor 蒋宇秋D·C·迪隆J·L·米查姆徐江春S·L·哈洛克W·T·海普勒
Owner CORIXA CORP
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