This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, J. Articles by Celis, E. Search for Related Content PubMed PubMed Citation Articles by Lu, J. Articles by Celis, E.

Use of Two Predictive Algorithms of the World Wide Web for the Identification of Tumor-reactive T-Cell Epitopes¹

Department of Immunology and Cancer Center, Mayo Clinic and Mayo Graduate School, Rochester, Minnesota 55905

Tumor cells can be effectively recognized and eliminated by CTLs. One approach for the development of CTL-based cancer immunotherapy for solid tumors requires the use of the appropriate immunogenic peptide epitopes that are derived from defined tumor-associated antigens. Because CTL peptide epitopes are restricted to specific MHC alleles, to design immune therapies for the general population it is necessary to identify epitopes for the most commonly found human MHC alleles. The identification of such epitopes has been based on MHC-peptide-binding assays that are costly and labor-intensive. We report here the use of two computer-based prediction algorithms, which are readily available in the public domain (Internet), to identify HLA-B7-restricted CTL epitopes for carcinoembryonic antigen (CEA). These algorithms identified three candidate peptides that we studied for their capacity to induce CTL responses in vitro using lymphocytes from HLA-B7+ normal blood donors. The results show that one of these peptides, CEA9₆₃₂ (IPQQHTQVL) was efficient in the induction of primary CTL responses when dendritic cells were used as antigen-presenting cells. These CTLs were efficient in killing tumor cells that express HLA-B7 and produce CEA. The identification of this HLA-B7-restricted CTL epitope will be useful for the design of ethnically unbiased, widely applicable immunotherapies for common solid epithelial tumors expressing CEA. Moreover, our strategy of identifying MHC class I-restricted CTL epitopes without the need of peptide/HLA-binding assays provides a convenient and cost-saving alternative approach to previous methods.

This article has been cited by other articles:

				K. H. Park, E. Gad, V. Goodell, Y. Dang, T. Wild, D. Higgins, P. Fintak, J. Childs, C. dela Rosa, and M. L. Disis Insulin-like Growth Factor-Binding Protein-2 Is a Target for the Immunomodulation of Breast Cancer Cancer Res., October 15, 2008; 68(20): 8400 - 8409. [Abstract] [Full Text] [PDF]

				C. Palena, D. E. Polev, K. Y. Tsang, R. I. Fernando, M. Litzinger, L. L. Krukovskaya, A. V. Baranova, A. P. Kozlov, and J. Schlom The Human T-Box Mesodermal Transcription Factor Brachyury Is a Candidate Target for T-Cell-Mediated Cancer Immunotherapy Clin. Cancer Res., April 15, 2007; 13(8): 2471 - 2478. [Abstract] [Full Text] [PDF]

				A. Boesen, K. Sundar, and R. Coico Lassa Fever Virus Peptides Predicted by Computational Analysis Induce Epitope-Specific Cytotoxic-T-Lymphocyte Responses in HLA-A2.1 Transgenic Mice Clin. Vaccine Immunol., October 1, 2005; 12(10): 1223 - 1230. [Abstract] [Full Text] [PDF]

				D. A. Rodeberg, R. A. Nuss, S. F. Elsawa, and E. Celis Recognition of Six-Transmembrane Epithelial Antigen of the Prostate-Expressing Tumor Cells by Peptide Antigen-Induced Cytotoxic T Lymphocytes Clin. Cancer Res., June 15, 2005; 11(12): 4545 - 4552. [Abstract] [Full Text] [PDF]

				A. M. Thomas, L. M. Santarsiero, E. R. Lutz, T. D. Armstrong, Y.-C. Chen, L.-Q. Huang, D. A. Laheru, M. Goggins, R. H. Hruban, and E. M. Jaffee Mesothelin-specific CD8+ T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients J. Exp. Med., August 2, 2004; 200(3): 297 - 306. [Abstract] [Full Text] [PDF]

				M. Ruiz, H. Kobayashi, J. J. Lasarte, J. Prieto, F. Borras-Cuesta, E. Celis, and P. Sarobe Identification and Characterization of a T-Helper Peptide from Carcinoembryonic Antigen Clin. Cancer Res., April 15, 2004; 10(8): 2860 - 2867. [Abstract] [Full Text] [PDF]

				A. W. Purcell and J. J. Gorman Immunoproteomics: Mass Spectrometry-based Methods to Study the Targets of the Immune Response Mol. Cell. Proteomics, March 1, 2004; 3(3): 193 - 208. [Abstract] [Full Text] [PDF]

				V. Ramakrishna, M. M. Ross, M. Petersson, C. C. Gatlin, C. E. Lyons, C. L. Miller, H. E. Myers, M. McDaniel, L. R. Karns, R. Kiessling, et al. Naturally occurring peptides associated with HLA-A2 in ovarian cancer cell lines identified by mass spectrometry are targets of HLA-A2-restricted cytotoxic T cells Int. Immunol., June 1, 2003; 15(6): 751 - 763. [Abstract] [Full Text] [PDF]

				A. Admon, E. Barnea, and T. Ziv Tumor Antigens and Proteomics from the Point of View of the Major Histocompatibility Complex Peptides Mol. Cell. Proteomics, June 1, 2003; 2(6): 388 - 398. [Abstract] [Full Text] [PDF]

				J. Lu, R. L. Giuntoli II, R. Omiya, H. Kobayashi, R. Kennedy, and E. Celis Interleukin 15 Promotes Antigen-independent in Vitro Expansion and Long-Term Survival of Antitumor Cytotoxic T Lymphocytes Clin. Cancer Res., December 1, 2002; 8(12): 3877 - 3884. [Abstract] [Full Text] [PDF]

				J. Lu and E. Celis Recognition of Prostate Tumor Cells by Cytotoxic T Lymphocytes Specific for Prostate-specific Membrane Antigen Cancer Res., October 15, 2002; 62(20): 5807 - 5812. [Abstract] [Full Text] [PDF]

				H. Kobayashi, R. Omiya, M. Ruiz, E. Huarte, P. Sarobe, J. J. Lasarte, M. Herraiz, B. Sangro, J. Prieto, F. Borras-Cuesta, et al. Identification of an Antigenic Epitope for Helper T Lymphocytes from Carcinoembryonic Antigen Clin. Cancer Res., October 1, 2002; 8(10): 3219 - 3225. [Abstract] [Full Text] [PDF]

				R. Omiya, C. Buteau, H. Kobayashi, C. V. Paya, and E. Celis Inhibition of EBV-Induced Lymphoproliferation by CD4+ T Cells Specific for an MHC Class II Promiscuous Epitope J. Immunol., August 15, 2002; 169(4): 2172 - 2179. [Abstract] [Full Text] [PDF]

				C. Buteau, S. N. Markovic, and E. Celis Challenges in the Development of Effective Peptide Vaccines for Cancer Mayo Clin. Proc., April 1, 2002; 77(4): 339 - 349. [Abstract] [PDF]

				R. L. Giuntoli II, J. Lu, H. Kobayashi, R. Kennedy, and E. Celis Direct Costimulation of Tumor-reactive CTL by Helper T Cells Potentiate Their Proliferation, Survival, and Effector Function Clin. Cancer Res., March 1, 2002; 8(3): 922 - 931. [Abstract] [Full Text] [PDF]

				H. Kobayashi, Y. Song, D. S. B. Hoon, E. Appella, and E. Celis Tumor-reactive T Helper Lymphocytes Recognize a Promiscuous MAGE-A3 Epitope Presented by Various Major Histocompatibility Complex Class II Alleles Cancer Res., June 1, 2001; 61(12): 4773 - 4778. [Abstract] [Full Text] [PDF]