Abstract
The general approach, termed reverse immunology, to predict and identify immunogenic peptides from the sequence of a gene product of interest has been postulated to be a particularly efficient, high-throughput approach to discover tumor antigens. This laboratory has successfully identified immunogenic peptides of the human telomerase reverse transcriptase (hTERT), a self-tumor antigen, by using a multi-step approach. These steps include the following: the use of predictive bioinformatics algorithms, molecular methods to identify tumor-specific transcripts, prediction of proteasomal cleavage sites, peptide-binding prediction to HLA molecules and experimental validation, assessment of the in vitro and in vivo immunogenic potential of selected peptide antigens, isolation of specific cytolytic T lymphocyte clones, and final validation in functional assays of tumor cell recognition. This laboratory, and others have used similar methods to identify immunogenic peptides of self-tumor antigens, and many of those peptides are included in vaccines currently tested in clinical trials.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Sette, A., and Sidney, J. (1999) Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism. Immunogenetics 50, 201–212.
Sette, A., Keogh, E., Ishioka, G., Sidney, J., Tangri, S., Livingston, B., McKinney, D., Newman, M., Chesnut, R., and Fikes, J. (2002) Epitope identification and vaccine design for cancer immunotherapy. Curr Opin Investig Drugs 3, 132–139.
Minev, B., Hipp, J., Firat, H., Schmidt, J. D., Langlade-Demoyen, P., and Zanetti, M. (2000) Cytotoxic T cell immunity against telomerase reverse transcriptase in humans. Proc Natl Acad Sci U S A 97, 4796–4801.
Vonderheide, R. H., Schultze, J. L., Anderson, K. S., Maecker, B., Butler, M. O., Xia, Z., Kuroda, M. J., von Bergwelt-Baildon, M. S., Bedor, M. M., Hoar, K. M., Schnipper, D. R., Brooks, M. W., Letvin, N. L., Stephans, K. F., Wucherpfennig, K. W., Hahn, W. C., and Nadler, L. M. (2001) Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals. Cancer Res 61, 8366–8370.
Hernandez, J., Garcia-Pons, F., Lone, L. C., Firat, H., Schmidt, J. D., Langlade-Demoyen, P., and Zanetti, M. (2002) Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA-A2.1 that induces CTL and mediates lysis of tumor cells. Proc Natl Acad Sci U S A 99, 12275–12280.
Hernandez, J., Schoeder, K., Blondelle, S. E., Pons, F. G., Lone, Y. C., Simora, A., Langlade-Demoyen, P., Wilson, D. B., and Zanetti, M. (2004) Antigenicity and immunogenicity of peptide analogues of a low affinity peptide of the human telomerase reverse transcriptase tumor antigen. Eur J Immunol 34, 2331–2341.
Gross, D. A., Graff-Dubois, S., Opolon, P., Cornet, S. S., Alves, P., Bennaceur-Griscelli, A., Faure, O., Guillaume, P., Firat, H. H., Chouaib, S., Lemonnier, F. A., Davoust, J., Miconnet, I., Vonderheide, R. H., and Kosmatopoulos, K. (2004) High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy. J Clin Invest 113, 425–433.
Zanetti, M. (2003) Protocol #0207-545: a phase I, escalating dose, open-label evaluation of safety, feasibility, and tolerability of transgenic lymphocyte immunization (TLI) vaccine subjects with histologically proven prostate adenocarcinoma. Hum Gene Ther 14, 301–302.
Cortez-Gonzalez, X., and Zanetti, M. (2007) Telomerase immunity from bench to bedside: round one. J Transl Med 5, 12.
Zanetti, M., Hernandez, X., and Langlade-Demoyen, P. (2005) Telomerase reverse transcriptase as target for anti-tumor T cell responses in humans. Springer Semin Immunopathol 27, 87–104.
Vonderheide, R. H., Domchek, S. M., Schultze, J. L., George, D. J., Hoar, K. M., Chen, D. Y., Stephans, K. F., Masutomi, K., Loda, M., Xia, Z., Anderson, K. S., Hahn, W. C., and Nadler, L. M. (2004) Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res 10, 828–839.
Cortez-Gonzalez, X., Sidney, J., Adotevi, O., Sette, A., Millard, F., Lemmonier, F., Langlade-Demoyen, P., and Zanetti, M. (2006) Immunogenic HLA-B7 restricted peptides of hTRT. Int Immunol 18, 1707–1718.
Parker, K. C., Bednarek, M. A., and Coligan, J. E. (1994) Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. Journal of Immunology 152, 163–175.
Rammensee, H. G., Friede, T., and Stevanoviic, S. (1995) MHC ligands and peptide motifs: first listing. Immunogenetics 41, 178–228.
Rammensee, H., Bachmann, J., Emmerich, N. P., Bachor, O. A., and Stevanovic, S. (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50, 213–219.
Kuttler, C., Nussbaum, A. K., Dick, T. P., Rammensee, H. G., Schild, H., and Hadeler, K. P. (2000) An algorithm for the prediction of proteasomal cleavages. J Mol Biol 298, 417–429.
Nussbaum, A. K., Kuttler, C., Hadeler, K. P., Rammensee, H. G., and Schild, H. (2001) PAProC: a prediction algorithm for proteasomal cleavages available on the http://WWW. Immunogenetics 53, 87–94.
Nielsen, M., Lundegaard, C., Lund, O., and Kesmir, C. (2005) The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage. Immunogenetics 57, 33–41.
Firat, H., Garcia-Pons, F., tourdot, S., Pascolo, S., Scardino, A., Garcia, Z., Michel, M.-L., Jack, R., Jung, G., Kostmatopoulos, K., Mateo, L., Suhbrbier, A., Lemonnier, F., and Langlade-Demoyen, P. (1999) H-2 class I knockout, HLA-A2.1-transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies. Eur. J. Immunol. 29, 3112–3121.
Sidney, J., del Guercio, M. F., Southwood, S., Engelhard, V. H., Appella, E., Rammensee, H. G., Falk, K., Rotzschke, O., Takiguchi, M., Kubo, R. T., and et al. (1995) Several HLA alleles share overlapping peptide specificities. J Immunol 154, 247–259.
Sidney, J., Southwood, S., del Guercio, M. F., Grey, H. M., Chesnut, R. W., Kubo, R. T., and Sette, A. (1996) Specificity and degeneracy in peptide binding to HLA-B7-like class I molecules. J Immunol 157, 3480–3490.
Sidney, J., Southwood, S., Oseroff, C., del Guercio, M. F., Sette, A., and Grey, H. M. (2001) Measurement of MHC/peptide interactions by gel filtration. Curr Protoc Immunol Chapter 18, Unit 18 13.
Schiewe, A. J., and Haworth, I. S. (2007) Structure-based prediction of MHC-peptide association: algorithm comparison and application to cancer vaccine design. J Mol Graph Model 26, 667–675.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Cortez-Gonzalez, X., Zanetti, M. (2010). Identification of Immunogenic Peptides of the Self-Tumor Antigen: Our Experience with Telomerase Reverse Transcriptase. In: Yotnda, P. (eds) Immunotherapy of Cancer. Methods in Molecular Biology, vol 651. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-786-0_12
Download citation
DOI: https://doi.org/10.1007/978-1-60761-786-0_12
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-785-3
Online ISBN: 978-1-60761-786-0
eBook Packages: Springer Protocols