Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma

Unwin, R. D., Harnden, P., Pappin, D., Rahman, D., Whelan, P., Craven, R. A., Selby, P. J., Banks, R. E. (January 2003) Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma. Proteomics, 3 (1). pp. 45-55. ISSN 1615-9853 (Print)1615-9853 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/12548633
DOI: 10.1002/pmic.200390008

Abstract

Renal cell carcinoma (RCC) is relatively resistant to conventional chemotherapy and radiotherapy. However, reports of spontaneous regression along with promising results in clinical trials suggest that immunotherapuetic strategies may be of clinical benefit. Few RCC related antigens have been identified to date, and the technical difficulty and time constraints of current antigen identification techniques preclude the screening of large numbers of patients. A comparatively rapid strategy has been used to identify components of tumors that elicit an antibody response in the patient - the serological and proteomic evaluation of antibody responses (SPEAR) approach. This combines two-dimensional polyarylamide gel electrophoresis of tumor and normal kidney samples with immunoblotting using autologous patient sera and protein identification by mass spectrometry. Using the SPEAR approach to screen RCC patients for naturally occurring antitumor antibody responses, a number of candidate immunogens have been identified in patients with high-grade disease and their relative expression levels in tumor tissue compared to normal tissue have been studied. These proteins include annexins I and IV, thymidine phosphorylase (TP), carbonic anhydrase I, Mn-superoxide dismutase and major vault protein (MVP). Downstream analysis of the tissue expression of some of these proteins shows that MVP is up-regulated in 2/4 of RCC tumors but is also expressed in normal kidney whereas TP is up-regulated in 100% (11/11) of RCC cases examined with no or minimal expression in normal kidney, indicating a potential use as a therapeutic target.

Item Type: Paper
Uncontrolled Keywords: Annexins/immunology Antibodies, Neoplasm/ biosynthesis/blood Antigens, Neoplasm/isolation & purification Cancer Vaccines/isolation & purification Carbonic Anhydrase I/immunology Carcinoma, Renal Cell/ immunology/therapy Electrophoresis, Gel, Two-Dimensional Humans Immunohistochemistry Immunotherapy Kidney Neoplasms/ immunology/therapy Proteome/ immunology/isolation & purification Superoxide Dismutase/immunology Vault Ribonucleoprotein Particles/immunology
Subjects: diseases & disorders > cancer
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: January 2003
Date Deposited: 01 Jul 2013 19:49
Last Modified: 01 Jul 2013 19:49
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27877

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