Telomerase immunity from bench to bedside: round one
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BioMed Central
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Telomerase immunity from bench to bedside: round one Xochtil Cortez-Gonzalez and Maurizio Zanetti* Address: The Laboratory of Immunology Department of Medicine and Moores Cancer Center University of California, San Diego 9500 Gilman Drive La Jolla, CA 92093-0837, USA Email: Xochtil Cortez-Gonzalez - [email protected]; Maurizio Zanetti* - [email protected] * Corresponding author
Published: 26 February 2007 Journal of Translational Medicine 2007, 5:12
doi:10.1186/1479-5876-5-12
Received: 18 November 2006 Accepted: 26 February 2007
This article is available from: http://www.translational-medicine.com/content/5/1/12 © 2007 Cortez-Gonzalez and Zanetti; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Telomerase, a reverse transcriptase primarily devoted to the elongation of telomeres in mammalian cells, is also the first bona fide common tumor antigen. In fact, telomerase is overexpressed in > 85% of tumor cells irrespective of origin and histological type. In the past seven years, there has been considerable interest in assessing telomerase as substrate for vaccination in cancer patients to induce CD8 T cell responses. Because the activation of T cells is restricted by the MHC molecules on antigen presenting cells or tumor cells, the identification of telomerase peptides immunogenic for humans is tightly linked with HLA types. To date, a handful of peptides have been identified through a variety of screening procedures, including bioinformatics prediction, in vivo immunization of HLA transgenic mice, in vitro immunization of PBMC from normal donors and cancer patients, and processing in human tumor cells. Currently, there exist putative peptides for five major HLA types (A2, A1, A3, A24 and B7). Due to the complexity of the HLA system, trials have been performed focusing on the most prevalent HLA type, HLA-A2. Here, we summarize this collective effort and highlight results obtained in Phase 1 trials including a Phase 1 trial performed at the UCSD Cancer Center.
Background Active immunization (vaccination) offers the greatest advantages to prevent or control disease. Applied to the control of cancer, this concept is referred to as therapeutic vaccination. In the past decade great effort was placed exerted to identify tumor associated and tumor specific antigens [1,2] and to develop efficient methods to vaccinate cancer patients [3-6]. By and large, efforts have been directed at inducing T cell mediated responses, and particularly major histocompatibility complex (MHC) Class Irestricted cytotoxic CD8 T lymphocytes. Tumor associated antigens can be clustered in major categories. Traditionally, they were regarded as onco-developmental antigens mainly carbohydrate in nature [7]. Subsequently, new families of antigens were ide
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