Resolving conflicting data on expression of the Tn antigen and implications for clinical trials with cancer vaccines
Open Access
- 1 April 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 8 (4), 971-979
- https://doi.org/10.1158/1535-7163.mct-08-0934
Abstract
The tumor-associated Tn antigen has been investigated extensively as a biomarker and therapeutic target. Cancer vaccines containing the Tn antigen as a single tumor antigen or as a component of a polyvalent vaccine have progressed into phase I and II clinical trials. One major focus of Tn-based vaccines is the treatment of prostate cancer patients. Although expression of the antigen on prostate tumors is a critical prerequisite, previous reports investigating Tn expression in prostate tumors have produced conflicting results. Using a combination of immunohistochemistry and carbohydrate microarray profiling, we show that only 4% to 26% of prostate tumors express the Tn antigen. Based on our results, the majority of prostate cancer patients do not express the appropriate antigen. Therefore, efforts to preselect the subset of prostate cancer patients with Tn-positive tumors or apply Tn vaccines to other cancers with higher rates of antigen expression could significantly improve clinical response rates. Because conflicting information on carbohydrate expression is a general problem for the field, the approach described in this article of analyzing antigen expression with multiple antibodies and using carbohydrate microarray profiles to interpret the results will be useful for the development of other carbohydrate-based cancer vaccines and diagnostics.[Mol Cancer Ther 2009;8(4):971–9)Keywords
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This publication has 50 references indexed in Scilit:
- Improved Procedure for Direct Coupling of Carbohydrates to Proteins via Reductive AminationBioconjugate Chemistry, 2008
- Robust immune responses elicited by a fully synthetic three-component vaccineNature Chemical Biology, 2007
- High‐Throughput Carbohydrate Microarray Analysis of 24 LectinsAngewandte Chemie-International Edition, 2006
- Carbohydrate vaccines as immunotherapy for cancerImmunology & Cell Biology, 2005
- Induction of carbohydrate‐specific antibodies in HLA‐DR transgenic mice by a synthetic glycopeptide: a potential anti cancer vaccine for human useChemical Biology & Drug Design, 2003
- MUCIN-TYPEO-GLYCOSYLATION IN HELMINTH PARASITES FROM MAJOR TAXONOMIC GROUPS: EVIDENCE FOR WIDESPREAD DISTRIBUTION OF THE TN ANTIGEN (GALNAC-SER/THR) AND IDENTIFICATION OF UDP-GALNAC:POLYPEPTIDEN-ACETYLGALACTOSAMINYLTRANSFERASE ACTIVITYJournal of Parasitology, 2003
- Immunoreactive T and Tn antigens in malignancy: role in carcinoma diagnosis, prognosis, and immunotherapyTransfusion Medicine Reviews, 2000
- Distribution of Tn antigen recognized by an anti-Tn monoclonal antibody (MLS128) in normal and malignant tissues of the digestive tractZeitschrift für Krebsforschung und Klinische Onkologie, 1995
- Human lung adenocarcinoma cell lines with different lung colonization potential (LCP), and a correlation between expression of sialosyl dimeric Lex (defined by MAb FH6) and LCPClinical & Experimental Metastasis, 1991
- Carbon-13 NMR studies of native and modified ovine submaxillary mucinBiochemistry, 1984