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Compositions and methods for the therapy and diagnosis of ovarian cancer

a technology for ovarian cancer and compositions, applied in the field of ovarian cancer therapy, can solve the problems of difficult interpretation, no vaccine or other universally successful method of prevention or treatment is currently available, and ovarian cancer is a significant health problem

Inactive Publication Date: 2008-09-18
CORIXA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The compositions effectively stimulate an immune response, potentially leading to improved treatment and prevention of ovarian cancer by targeting specific ovarian tumor antigens, offering a more effective approach than existing therapies.

Problems solved by technology

Ovarian cancer is a significant health problem for women in the United States and throughout the world.
Although advances have been made in detection and therapy of this cancer, no vaccine or other universally successful method for prevention or treatment is currently available.
However, the use of established markers often leads to a result that is difficult to interpret, and high mortality continues to be observed in many cancer patients.
However, to date, relatively few ovarian carcinoma antigens are known and the generation of an immune response against such antigens has not been shown to be therapeutically beneficial.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Identification of Representative Ovarian Carcinoma cDNA Sequences

[0373]Primary ovarian tumor and metastatic ovarian tumor cDNA libraries were each constructed in kanamycin resistant pZErO™-2 vector (Invitrogen) from pools of three different ovarian tumor RNA samples. For the primary ovarian tumor library, the following RNA samples were used: (1) a moderately differentiated papillary serous carcinoma of a 41 year old, (2) a stage IIIC ovarian tumor and (3) a papillary serous adenocarcinoma for a 50 year old Caucasian. For the metastatic ovarian tumor library, the RNA samples used were omentum tissue from: (1) a metastatic poorly differentiated papillary adenocarcinoma with psammoma bodies in a 73 year old, (2) a metastatic poorly differentiated adenocarcinoma in a 74 year old and (3) a metastatic poorly differentiated papillary adenocarcinoma in a 68 year old.

[0374]The number of clones in each library was estimated by plating serial dilutions of unamplified libraries. Insert data wer...

example 2

Analysis of cDNA Expression Using Microarray Technology

[0387]In additional studies, sequences disclosed herein were found to be overexpressed in specific tumor tissues as determined by microarray analysis. Using this approach, cDNA sequences are PCR amplified and their mRNA expression profiles in tumor and normal tissues are examined using cDNA microarray technology essentially as described (Shena et al., 1995). In brief, the clones are arrayed onto glass slides as multiple replicas, with each location corresponding to a unique cDNA clone (as many as 5500 clones can be arrayed on a single slide or chip). Each chip is hybridized with a pair of cDNA probes that are fluorescence-labeled with Cy3 and Cy5 respectively. Typically, 1 μg of polyA+ RNA is used to generate each cDNA probe. After hybridization, the chips are scanned and the fluorescence intensity recorded for both Cy3 and Cy5 channels. There are multiple built-in quality control steps. First, the probe quality is monitored usi...

example 3

Expression of Recombinant Antigen O568S in E. coli

[0392]This example describes the expression of recombinant antigen O568S (SEQ ID NO:177) in E. coli. This sequence was identified in Example 1 from the POTS 7 subtraction library using primary ovarian tumor cDNA as the tracer. PCR primers specific for the open reading frame of O568S were designed and used in the specific amplification of O568S. The PCR product was enzymatically digested with EcoRI and ligated into PPDM, a modified pET28 vector which had been cut with the restriction enzymes EcoRI and Eco72I. The construct sequence and orientation was confirmed through sequence analysis, the sequence of which is shown in SEQ ID NO:206. The vector was then transformed into the expression hosts, BLR (DE3) and HMS174 (DE3) pLys S. Protein expression was confirmed, the sequence of which is provided in SEQ ID NO:207.

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PUM

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Abstract

Compositions and methods for the therapy and diagnosis of cancer, particularly ovarian cancer, are disclosed. Illustrative compositions comprise one or more ovarian tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and / or treatment of diseases, particularly ovarian cancer.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 11 / 250,759, filed on Oct. 14, 2005, now pending; which is a continuation of U.S. application Ser. No. 10 / 369,186, filed on Feb. 14, 2003, now abandoned; which is a continuation-in-part of U.S. application Ser. No. 10 / 361,811, filed on Feb. 5, 2003, now abandoned; which is a continuation-in-part of U.S. application Ser. No. 10 / 212,677, filed on Aug. 2, 2002, now abandoned; which is a continuation-in-part of U.S. application Ser. No. 09 / 970,966, filed on Oct. 2, 2001, now U.S. Pat. No. 6,720,146; which is a continuation-in-part of U.S. application Ser. No. 09 / 825,294, filed on Apr. 3, 2001, now U.S. Pat. No. 6,710,170; which is a continuation-in-part of U.S. application Ser. No. 09 / 713,550, filed on Nov. 14, 2000, now U.S. Pat. No. 6,617,109; which is a continuation-in-part of U.S. application Ser. No. 09 / 656,668, filed on Sep. 7, 2000, now abandoned; which is a continuation-in...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395C07H21/04C12N15/00C12N5/00C12Q1/68A61K48/00C07K16/00G01N33/53C12N5/06A61K38/00A61K39/00C07K14/47
CPCA61K38/00A61K39/0011A61K2039/505C07K14/47C07K14/4748Y10T436/25375C12Q1/6886G01N33/57449Y10T436/25125Y10T436/255Y10T436/25C07K16/3069C12Q2600/158C07K2317/34A61P35/00
Inventor FANGER, GARY R.FLING, STEVEN P.
Owner CORIXA CORP