Detection and treatment of cancers of the lung

a lung cancer and lung cancer technology, applied in the field of cancer therapies and diagnostics, can solve the problems of cancer, or malignancy, crowding out healthy cells, invasive biopsies, and inability to detect cancers,

Inactive Publication Date: 2007-01-04
HANASH SAMIR M +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007] There is increasing evidence for an immune response to cancer in humans, demonstrated by the identification of autoantibodies to tumor antigens (Stocket et al., J. Exp. Med., 187:1349 [1998]; Boon and Old, Curr. Opin. Immunol. 9:681 [1997]; Soussl, Cancer Res. 60:1777 [2000]; Old and Chen, J. Exp. Med. 187:1163 [1998]). The identification of panels of tumor antigens that elicit a humoral response has utility in cancer screening, diagnosis, and in establishing a prognosis. Such antigens also have utility in immunotherapy against cancers. Several approaches are currently available for the identification of tumor antigens. The present invention provides a proteomic-based approach for the identification of tumor antigens that induce an antibody response. In contrast to other approaches based on the analysis of recombinant proteins, a proteomic approach allows identification of autoantibodies to proteins that are directly derived from cancer cells or tumors and thus may uncover antigenicity associated with post-translational modification.
[0018] The terms “specific binding” or “specifically binding” when used in reference to the interaction of an antibody and a protein or peptide means that the interaction is dependent upon the presence of a particular structure (i.e., the antigenic determinant or epitope) on the protein; in other words the antibody is recognizing and binding to a specific protein structure rather than to proteins in general. For example, if an antibody is specific for epitope “A,” the presence of a protein containing epitope A (or free, unlabelled A) in a reaction containing labeled “A” and the antibody will reduce the amount of labeled A bound to the antibody.

Problems solved by technology

But cancerous, or malignant, tumors continue to grow, crowding out healthy cells, interfering with body functions, and drawing nutrients away from body tissues.
However, many biopsies are invasive, unpleasant procedures with their own associated risks, such as pain, bleeding, infection, and tissue or organ damage.
In addition, if a biopsy does not result in an accurate or large enough sample, a false negative or misdiagnosis can result, often requiring that the biopsy be repeated.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Experimental Methods

A. Tissue and Serum Specimens

[0215] Tumor tissue and sera were obtained at the time of diagnosis following informed consent. The experimental protocol was approved by the University of Michigan Institutional Review Board. Sera from 64 lung cancer patients were analyzed. This patient population consisted approximately equally of males and females with an age range of 46 to 82 (median, 64.6 years). Of 64 cases, there were 40 with adenocarcinoma, 18 with squamous cell carcinoma, 4 with SCLC and 2 with large cell carcinoma, all histologically confirmed. Sera from 99 patients with other types of cancer, including 44 with liver cancer, 11 with breast cancer, 14 with brain tumor, 23 with neuroblastoma, and 7 with melanoma were also investigated. Non-cancer controls included 61 healthy subjects without a prior history of cancer or autoimmune disease, and 10 other subjects with chronic lung disease.

B. PAGE and Western Blotting

[0216] Following excision, tumor tissue...

example 2

Reactivity of Sera from Lung Cancer Patients with PGP 9.5

[0221] Sera obtained at the time of diagnosis from 64 patients with lung cancer were investigated for the presence of IgG antibodies to A549 adenocarcinoma cell line proteins. Serum from 9 of 64 patients with lung cancer (Table 1), including 6 sera from patients with adenocarcinoma, 2 with squamous cell carcinoma and one with SCLC, exhibited IgG based reactivity against a group of 3 proteins with an estimated MW of 25 kDa and with a pI between 5.0 and 5.6. Tumor stage information was available for 30 patients with adenocarcinoma (22 stage I, 4 stage II, 3 stage III and 1 stage IV). In this subset, two patients with stage I and one with stage II had autoantibodies to the group of three proteins, suggesting that the occurrence of antibodies was not a feature of advanced stage disease. Likewise, the two patients with squamous cell carcinoma and positive sera had stage I disease. Sera from lung cancer patients that exhibited IgG...

example 3

Expression of PGP 9.5 Protein in Lung Tissue

[0224] Increased levels of PGP 9.5 mRNA and protein have been previously reported in non-small cell lung cancer tissue based on Serial Analysis of Gene Expression (SAGE) and immunochemistry (Hibi et al., Cancer Res., 58:5690 [1998; Hibi et al., am. J. Pathol., 155:711 [1999]). Given the occurrence of multiple isoforms of PGP 9.5 protein in A549 adenocarcinoma cell lysates, PGP 9.5 expression in lung tumors and in normal lung using 2-D PAGE was analyzed in order to investigate differential expression of PGP 9.5 isoforms. 2-D PAGE and silver staining protein patterns corresponding to 82 lung tumors (33 adenocarcinomas, 27 squamous cell carcinomas, 15 SCLC and 7 neuroendocrine differentiated adenocarcinomas) and adjacent normal lung for 16 tumors were analyzed. PGP 9.5 protein was detected in 100% of small cell carcinomas, 63% (21 / 33) of adenocarcinomas, 85% (23 / 27) of squamous cell carcinomas and 100% of neuroendocrine differentiated adeno...

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PUM

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Abstract

The present invention relates to compositions and methods for cancer therapies and diagnostics, including but not limited to, cancer markers. In particular, the present invention provides tumor antigens associated with specific cancers and diagnostic assays for the detection of such antigens and associated autoantibodies as indicative of the presence of specific cancers. The present invention further provides cancer immunotherapy utilizing the tumor antigens of the present invention.

Description

[0001] This application claims priority to provisional patent application serial number 60 / 323,505, filed Sep. 19, 2001. This invention was made with government support under Grant No. CA84982 awarded by the National Institutes of Health. The Government may have certain rights in the invention.FIELD OF THE INVENTION [0002] The present invention relates to compositions and methods for cancer therapies and diagnostics, including but not limited to, cancer markers. In particular, the present invention provides tumor antigens associated with specific cancers and diagnostic assays for the detection of such antigens and associated autoantibodies as indicative of the presence of lung cancers. BACKGROUND OF THE INVENTION [0003] The term cancer collectively refers to more than 100 different diseases that affect nearly every part of the body. Throughout life, healthy cells in the body divide, grow, and replace themselves in a controlled fashion. Cancer starts when the genes directing this cel...

Claims

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Application Information

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IPC IPC(8): C12Q1/68G01N33/574A61K39/00C07K14/47C07K16/30C12P21/08G01N33/564
CPCA61K39/0011A61K2039/55522G01N33/57423C07K16/3023G01N33/564C07K14/47
Inventor HANASH, SAMIR M.BRICHORY, FRANCK
Owner HANASH SAMIR M
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