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Compositions and methods for therapy and diagnosis of prostate cancer

A prostate tumor and sequence technology, applied in the fields of botanical equipment and methods, biochemical equipment and methods, chemical instruments and methods, etc., can solve the problems of difficult and effective diagnosis and treatment of prostate cancer, and does not show the level of metastasis

Inactive Publication Date: 2001-10-03
CORIXA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, PSA measurements correlate with prostate volume and do not reveal metastatic levels
[0004] Despite much research into treatments for these and other cancers, prostate cancer remains difficult to diagnose and treat effectively

Method used

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  • Compositions and methods for therapy and diagnosis of prostate cancer
  • Compositions and methods for therapy and diagnosis of prostate cancer
  • Compositions and methods for therapy and diagnosis of prostate cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0580] Isolation and Characterization of Prostate Tumor Peptides

[0581] This example describes the isolation of certain prostate tumor polypeptides from a prostate tumor cDNA library.

[0582] A human prostate tumor cDNA expression library was constructed from prostate tumor polyA+ RNA using the Superscript plasmid system for cDNA synthesis and plasmid cloning kit (BRLLife Technologies, Gaithersburg, MD 20897) according to the manufacturer's recommended method. Specifically, prostate tumor tissue was homogenized with polytron (Kinematica, Switzerland), and total RNA was extracted with Trizol reagent (BRL Life Technologies) according to the manufacturer's instructions. Then, poly A+ RNA was purified using Qiagen oligotex spin column mRNA purification kit (Qiagen, Santa Clarita, CA 91355) according to the manufacturer's recommended method. First-strand cDNA was synthesized with Not I / Oligo-dT18 primer. Double-stranded cDNA was synthesized, ligated with EcoRI / Ba...

Embodiment 2

[0601] Determination of tissue specificity of prostate tumor polypeptide

[0602] Using gene-specific primers, reverse transcription PCR was used to detect representative prostate tumor polypeptides F1-16, H1-1, J1-17 (also known as P502S), L1-12 (also known as P501S) in a variety of normal and tumor tissues. ), F1-12 (also known as P504S) and N1-1862 (also known as P503S) mRNA expression levels.

[0603] Briefly, total RNA was extracted from a variety of normal and tumor tissues using Trizol reagent as described above. 1-2 μg of total RNA was taken, and the first strand was synthesized at 42° C. for 1 hour using SuperScript II reverse transcriptase (BRL Life Technologies). The cDNA is then amplified by PCR using gene-specific primers. To ensure the semi-quantitative nature of reverse transcription PCR, β-actin was used as an internal control for each tissue tested. First, serial dilutions of first-strand cDNA were prepared for reverse transcription PCR detection ...

Embodiment 3

[0615] Isolation and identification of prostate tumor polypeptides by PCR-based subtraction

[0616] The cDNA subtraction library was purchased from Clontech, which contained 10 other normal tissue cDNAs (brain, heart, kidney, liver, lung, ovary, placenta, skeletal muscle, spleen and thymus) for subtraction, followed by the first Normal prostate cDNA amplified by rounds of PCR. This library was subjected to a second round of PCR amplification according to the manufacturer's recommended method. The resulting cDNA fragment was subcloned into the vector pT7 Blue T-vector (Novagen, Madison, WI) and transformed into XL-1 Blue MRF' E. coli (Stratagene). DNA was isolated from independent clones and sequenced using a Perkin Elmer / Applied Biosystems Division Automated Sequencer Model 373A.

[0617] 59 positive clones were sequenced. Comparing the DNA sequences of these clones with those in the above-mentioned gene bank showed no obvious homology with 25 of the clones, namely P5...

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Abstract

Compositions and methods for the therapy and diagnosis of cancer, such as prostate cancer, are disclosed. Compositions may comprise one or more prostate tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a prostate tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as prostate cancer. Diagnostic methods based on detecting a prostate tumor protein, or mRNA encoding such a protein, in a sample are also provided.

Description

technical field [0001] The present invention relates generally to the treatment and diagnosis of cancer, such as prostate cancer. More particularly, the present invention relates to polypeptides comprising at least a portion of prostate tumor protein and polynucleotides encoding these polypeptides. These polypeptides and polynucleotides can be used in vaccines and pharmaceutical compositions to prevent and treat prostate cancer, and to diagnose and monitor these cancers. Background of the invention [0002] Prostate cancer is the most common cancer in men, affecting an estimated 30% of men over the age of 50. Quite a lot of clinical evidence shows that human prostate cancer has a tendency to metastasize to bone, and the disease appears to inevitably develop from androgen-dependent state to androgen-refractory state, resulting in increased mortality of patients. This widespread disease is currently the second-highest cause of cancer death among America...

Claims

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Application Information

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IPC IPC(8): G01N33/574A61K38/00A61K39/00A61K39/395A61P35/00C07K14/47C07K16/30C12N5/10C12N15/09C12N15/12C12P21/08C12Q1/68G01N33/68
CPCC07K2319/00C07K14/4748A61K2039/5156A61K39/00A61P35/00A61K39/464493A61K39/4611A61K2239/58C07K14/435
Inventor D·C·迪隆S·L·哈洛克蒋宇秋徐江春J·L·米特查姆
Owner CORIXA CORP
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