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*
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland;
Unité 463, Institut National de la Santé et de la Recherche Médicale, Nantes, France;
Instituto de Parasitología y Biomedicina, Consejo Superior de Investigaciones Científicas, Granada, Spain;
§
Centre Pluridisciplinaire d’Oncologie, CHUV, Lausanne, Switzerland; and
¶
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
The Melan-A/MART-1 gene, which is expressed by normal melanocytes as well as by most fresh melanoma samples and melanoma cell lines, codes for Ags recognized by tumor-reactive CTL. HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A27-35 (AAGIGILTV) and the Melan-A26-35 (EAAGIGILTV) peptides. The sequences of these two peptides are not necessarily optimal as far as binding to HLA-A*0201 is concerned, since both lack one of the dominant anchor amino acid residues (leucine or methionine) at position 2. In this study we introduced single amino acid substitutions in either one of the two natural peptide sequences with the aim of improving peptide binding to HLA-A*0201 and/or recognition by specific CTL. Surprisingly, analogues of the Melan-A27-35 peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL. In contrast, among the Melan-A26-35 peptide analogues tested, the peptide ELAGIGILTV was not only able to display stable binding to HLA-A2.1 but was also recognized more efficiently than the natural peptide by two short-term cultured tumor-infiltrated lymph node cell cultures as well as by five of five tumor-reactive CTL clones. Moreover, in vitro generation of tumor-reactive CTL by stimulation of PBMC from HLA-A*0201 melanoma patients with this particular peptide analogue was much more efficient than that observed with either one of the two natural peptides. These results suggest that the Melan-A26-35 peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
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V. Rubio-Godoy, V. Dutoit, Y. Zhao, R. Simon, P. Guillaume, R. Houghten, P. Romero, J.-C. Cerottini, C. Pinilla, and D. Valmori Positional Scanning-Synthetic Peptide Library-Based Analysis of Self- and Pathogen-Derived Peptide Cross-Reactivity with Tumor-Reactive Melan-A-Specific CTL J. Immunol., November 15, 2002; 169(10): 5696 - 5707. [Abstract] [Full Text] [PDF]
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S. Mandruzzato, E. Rossi, F. Bernardi, V. Tosello, B. Macino, G. Basso, V. Chiarion-Sileni, C. R. Rossi, C. Montesco, and P. Zanovello Large and Dissimilar Repertoire of Melan-A/MART-1-Specific CTL in Metastatic Lesions and Blood of a Melanoma Patient J. Immunol., October 1, 2002; 169(7): 4017 - 4024. [Abstract] [Full Text] [PDF]
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J. Hernandez, F. Garcia-Pons, Y. C. Lone, H. Firat, J. D. Schmidt, P. Langlade-Demoyen, and M. Zanetti Identification of a human telomerase reverse transcriptase peptide of low affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of tumor cells PNAS, September 17, 2002; 99(19): 12275 - 12280. [Abstract] [Full Text] [PDF]
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S. Graff-Dubois, O. Faure, D.-A. Gross, P. Alves, A. Scardino, S. Chouaib, F. A. Lemonnier, and K. Kosmatopoulos Generation of CTL Recognizing an HLA-A*0201-Restricted Epitope Shared by MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 Tumor Antigens: Implication in a Broad-Spectrum Tumor Immunotherapy J. Immunol., July 1, 2002; 169(1): 575 - 580. [Abstract] [Full Text] [PDF]
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E. Huarte, P. Sarobe, J. Lu, N. Casares, J. J. Lasarte, J. Dotor, M. Ruiz, J. Prieto, E. Celis, and F. Borras-Cuesta Enhancing Immunogenicity of a CTL Epitope from Carcinoembryonic Antigen by Selective Amino Acid Replacements Clin. Cancer Res., July 1, 2002; 8(7): 2336 - 2344. [Abstract] [Full Text] [PDF]
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 G. Parmiani, C. Castelli, P. Dalerba, R. Mortarini, L. Rivoltini, F. M. Marincola, and A. Anichini Cancer Immunotherapy With Peptide-Based Vaccines: What Have We Achieved? Where Are We Going? J Natl Cancer Inst, June 5, 2002; 94(11): 805 - 818. [Abstract] [Full Text] [PDF]
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M. J. Palmowski, E. M.-L. Choi, I. F. Hermans, S. C. Gilbert, J.-L. Chen, U. Gileadi, M. Salio, A. Van Pel, S. Man, E. Bonin, et al. Competition Between CTL Narrows the Immune Response Induced by Prime-Boost Vaccination Protocols J. Immunol., May 1, 2002; 168(9): 4391 - 4398. [Abstract] [Full Text] [PDF]
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M. S. von Bergwelt-Baildon, R. H. Vonderheide, B. Maecker, N. Hirano, K. S. Anderson, M. O. Butler, Z. Xia, W. Y. Zeng, K. W. Wucherpfennig, L. M. Nadler, et al. Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: potential for clinical application Blood, May 1, 2002; 99(9): 3319 - 3325. [Abstract] [Full Text] [PDF]
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D. Valmori, V. Dutoit, V. Schnuriger, A.-L. Quiquerez, M. J. Pittet, P. Guillaume, V. Rubio-Godoy, P. R. Walker, D. Rimoldi, D. Lienard, et al. Vaccination with a Melan-A Peptide Selects an Oligoclonal T Cell Population with Increased Functional Avidity and Tumor Reactivity J. Immunol., April 15, 2002; 168(8): 4231 - 4240. [Abstract] [Full Text] [PDF]
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T. Luft, P. Luetjens, H. Hochrein, T. Toy, K.-A. Masterman, M. Rizkalla, C. Maliszewski, K. Shortman, J. Cebon, and E. Maraskovsky IFN-{alpha} enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells Int. Immunol., April 1, 2002; 14(4): 367 - 380. [Abstract] [Full Text] [PDF]
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V. Rubio-Godoy, C. Pinilla, V. Dutoit, E. Borras, R. Simon, Y. Zhao, J.-C. Cerottini, P. Romero, R. Houghten, and D. Valmori Toward Synthetic Combinatorial Peptide Libraries in Positional Scanning Format (PS-SCL)-based Identification of CD8+ Tumor-reactive T-Cell Ligands: A Comparative Analysis of PS-SCL Recognition by a Single Tumor-reactive CD8+ Cytolytic T-Lymphocyte Clone Cancer Res., April 1, 2002; 62(7): 2058 - 2063. [Abstract] [Full Text] [PDF]
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 H. Pilch, H. Hohn, K. Freitag, C. Neukirch, A. Necker, P. Haddad, B. Tanner, P. G. Knapstein, and M. J. Maeurer Improved Assessment of T-Cell Receptor (TCR) VB Repertoire in Clinical Specimens: Combination of TCR-CDR3 Spectratyping with Flow Cytometry-Based TCR VB Frequency Analysis Clin. Vaccine Immunol., March 1, 2002; 9(2): 257 - 266. [Abstract] [Full Text] [PDF]
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D. Valmori, C. Scheibenbogen, V. Dutoit, D. Nagorsen, A. M. Asemissen, V. Rubio-Godoy, D. Rimoldi, P. Guillaume, P. Romero, D. Schadendorf, et al. Circulating Tumor-reactive CD8+ T Cells in Melanoma Patients Contain a CD45RA+CCR7- Effector Subset Exerting ex Vivo Tumor-specific Cytolytic Activity Cancer Res., March 1, 2002; 62(6): 1743 - 1750. [Abstract] [Full Text] [PDF]
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 A. Zippelius, M. J. Pittet, P. Batard, N. Rufer, M. de Smedt, P. Guillaume, K. Ellefsen, D. Valmori, D. Lienard, J. Plum, et al. Thymic Selection Generates a Large T Cell Pool Recognizing a Self-Peptide in Humans J. Exp. Med., February 19, 2002; 195(4): 485 - 494. [Abstract] [Full Text] [PDF]
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V. Dutoit, V. Rubio-Godoy, M.-A. Doucey, P. Batard, D. Lienard, D. Rimoldi, D. Speiser, P. Guillaume, J.-C. Cerottini, P. Romero, et al. Functional Avidity of Tumor Antigen-Specific CTL Recognition Directly Correlates with the Stability of MHC/Peptide Multimer Binding to TCR J. Immunol., February 1, 2002; 168(3): 1167 - 1171. [Abstract] [Full Text] [PDF]
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I. Miconnet, S. Koenig, D. Speiser, A. Krieg, P. Guillaume, J.-C. Cerottini, and P. Romero CpG Are Efficient Adjuvants for Specific CTL Induction Against Tumor Antigen-Derived Peptide J. Immunol., February 1, 2002; 168(3): 1212 - 1218. [Abstract] [Full Text] [PDF]
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R. Campanelli, B. Palermo, S. Garbelli, S. Mantovani, P. Lucchi, A. Necker, E. Lantelme, and C. Giachino Human CD8 co-receptor is strictly involved in MHC-peptide tetramer-TCR binding and T cell activation Int. Immunol., January 1, 2002; 14(1): 39 - 44. [Abstract] [Full Text] [PDF]
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H. Terasawa, K.-Y. Tsang, J. Gulley, P. Arlen, and J. Schlom Identification and Characterization of a Human Agonist Cytotoxic T-Lymphocyte Epitope of Human Prostate-specific Antigen Clin. Cancer Res., January 1, 2002; 8(1): 41 - 53. [Abstract] [Full Text] [PDF]
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J.-S. Blanchet, D. Valmori, I. Dufau, M. Ayyoub, C. Nguyen, P. Guillaume, B. Monsarrat, J.-C. Cerottini, P. Romero, and J. E. Gairin A New Generation of Melan-A/MART-1 Peptides That Fulfill Both Increased Immunogenicity and High Resistance to Biodegradation: Implication for Molecular Anti-Melanoma Immunotherapy J. Immunol., November 15, 2001; 167(10): 5852 - 5861. [Abstract] [Full Text] [PDF]
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D. Rimoldi, K. Muehlethaler, S. Salvi, D. Valmori, P. Romero, J.-C. Cerottini, and F. Levy Subcellular Localization of the Melanoma-associated Protein Melan-AMART-1 Influences the Processing of Its HLA-A2-restricted Epitope J. Biol. Chem., November 9, 2001; 276(46): 43189 - 43196. [Abstract] [Full Text] [PDF]
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S. Tangri, G. Y. Ishioka, X. Huang, J. Sidney, S. Southwood, J. Fikes, and A. Sette Structural Features of Peptide Analogs of Human Histocompatibility Leukocyte Antigen Class I Epitopes That Are More Potent and Immunogenic than Wild-Type Peptide J. Exp. Med., September 17, 2001; 194(6): 833 - 846. [Abstract] [Full Text] [PDF]
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P. Sliz, O. Michielin, J.-C. Cerottini, I. Luescher, P. Romero, M. Karplus, and D. C. Wiley Crystal Structures of Two Closely Related but Antigenically Distinct HLA-A2/Melanocyte-Melanoma Tumor-Antigen Peptide Complexes J. Immunol., September 15, 2001; 167(6): 3276 - 3284. [Abstract] [Full Text] [PDF]
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T. Luft, M. Rizkalla, T. Y. Tai, Q. Chen, R. I. MacFarlan, I. D. Davis, E. Maraskovsky, and J. Cebon Exogenous Peptides Presented by Transporter Associated with Antigen Processing (TAP)-Deficient and TAP-Competent Cells: Intracellular Loading and Kinetics of Presentation J. Immunol., September 1, 2001; 167(5): 2529 - 2537. [Abstract] [Full Text] [PDF]
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C. Pinilla, V. Rubio-Godoy, V. Dutoit, P. Guillaume, R. Simon, Y. Zhao, R. A. Houghten, J.-C. Cerottini, P. Romero, and D. Valmori Combinatorial Peptide Libraries as an Alternative Approach to the Identification of Ligands for Tumor-reactive Cytolytic T Lymphocytes Cancer Res., July 1, 2001; 61(13): 5153 - 5160. [Abstract] [Full Text] [PDF]
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M. J. Pittet, A. Zippelius, D. E. Speiser, M. Assenmacher, P. Guillaume, D. Valmori, D. Lienard, F. Lejeune, J.-C. Cerottini, and P. Romero Ex Vivo IFN-{{gamma}} Secretion by Circulating CD8 T Lymphocytes: Implications of a Novel Approach for T Cell Monitoring in Infectious and Malignant Diseases J. Immunol., June 15, 2001; 166(12): 7634 - 7640. [Abstract] [Full Text] [PDF]
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I. Miconnet, I. Coste, F. Beermann, J.-F. Haeuw, J.-C. Cerottini, J.-Y. Bonnefoy, P. Romero, and T. Renno Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction J. Immunol., April 1, 2001; 166(7): 4612 - 4619. [Abstract] [Full Text] [PDF]
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P.-Y. Dietrich, P. R. Walker, A.-L. Quiquerez, G. Perrin, V. Dutoit, D. Liénard, P. Guillaume, J.-C. Cerottini, P. Romero, and D. Valmori Melanoma Patients Respond to a Cytotoxic T Lymphocyte-defined Self-Peptide with Diverse and Nonoverlapping T-Cell Receptor Repertoires Cancer Res., March 1, 2001; 61(5): 2047 - 2054. [Abstract] [Full Text]
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M. V. Dhodapkar, J. W. Young, P. B. Chapman, W. I. Cox, J. F. Fonteneau, S. Amigorena, A. N. Houghton, R. M. Steinman, and N. Bhardwaj Paucity of Functional T-Cell Memory to Melanoma Antigens in Healthy Donors and Melanoma Patients Clin. Cancer Res., December 1, 2000; 6(12): 4831 - 4838. [Abstract] [Full Text]
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P. R. Dunbar, C. L. Smith, D. Chao, M. Salio, D. Shepherd, F. Mirza, M. Lipp, A. Lanzavecchia, F. Sallusto, A. Evans, et al. A Shift in the Phenotype of Melan-A-Specific CTL Identifies Melanoma Patients with an Active Tumor-Specific Immune Response J. Immunol., December 1, 2000; 165(11): 6644 - 6652. [Abstract] [Full Text] [PDF]
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L. Jenne, J.-F. Arrighi, H. Jonuleit, J.-H. Saurat, and C. Hauser Dendritic Cells Containing Apoptotic Melanoma Cells Prime Human CD8+ T Cells for Efficient Tumor Cell Lysis Cancer Res., August 1, 2000; 60(16): 4446 - 4452. [Abstract] [Full Text]
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D. Valmori, V. Dutoit, D. Liénard, D. Rimoldi, M. J. Pittet, P. Champagne, K. Ellefsen, U. Sahin, D. Speiser, F. Lejeune, et al. Naturally Occurring Human Lymphocyte Antigen-A2 Restricted CD8+ T-Cell Response to the Cancer Testis Antigen NY-ESO-1 in Melanoma Patients Cancer Res., August 1, 2000; 60(16): 4499 - 4506. [Abstract] [Full Text]
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J.-L. Chen, P. R. Dunbar, U. Gileadi, E. Jager, S. Gnjatic, Y. Nagata, E. Stockert, D. L. Panicali, Y.-T. Chen, A. Knuth, et al. Identification of NY-ESO-1 Peptide Analogues Capable of Improved Stimulation of Tumor-Reactive CTL J. Immunol., July 15, 2000; 165(2): 948 - 955. [Abstract] [Full Text] [PDF]
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R. Mortarini, A. Borri, G. Tragni, I. Bersani, C. Vegetti, E. Bajetta, S. Pilotti, V. Cerundolo, and A. Anichini Peripheral Burst of Tumor-specific Cytotoxic T Lymphocytes and Infiltration of Metastatic Lesions by Memory CD8+ T Cells in Melanoma Patients Receiving Interleukin 12 Cancer Res., July 1, 2000; 60(13): 3559 - 3568. [Abstract] [Full Text]
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M. Oelke, U. Moehrle, J.-L. Chen, D. Behringer, V. Cerundolo, A. Lindemann, and A. Mackensen Generation and Purification of CD8+ Melan-A-specific Cytotoxic T Lymphocytes for Adoptive Transfer in Tumor Immunotherapy Clin. Cancer Res., May 1, 2000; 6(5): 1997 - 2005. [Abstract] [Full Text] [PDF]
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N. Gervois, N. Labarriere, S. Le Guiner, M.-C. Pandolfino, J.-F. Fonteneau, Y. Guilloux, E. Diez, B. Dreno, and F. Jotereau High Avidity Melanoma-reactive Cytotoxic T Lymphocytes Are Efficiently Induced from Peripheral Blood Lymphocytes on Stimulation by Peptide-pulsed Melanoma Cells Clin. Cancer Res., April 1, 2000; 6(4): 1459 - 1467. [Abstract] [Full Text]
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T. N. J. Bullock, T. A. Colella, and V. H. Engelhard The Density of Peptides Displayed by Dendritic Cells Affects Immune Responses to Human Tyrosinase and gp100 in HLA-A2 Transgenic Mice J. Immunol., March 1, 2000; 164(5): 2354 - 2361. [Abstract] [Full Text] [PDF]
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M. H. Andersen, L. O. Pedersen, J. C. Becker, and P. t. Straten Identification of a Cytotoxic T Lymphocyte Response to the Apoptosis Inhibitor Protein Survivin in Cancer Patients Cancer Res., February 1, 2000; 61(3): 869 - 872. [Abstract] [Full Text]
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D. Valmori, F. Levy, I. Miconnet, P. Zajac, G. C. Spagnoli, D. Rimoldi, D. Lienard, V. Cerundolo, J.-C. Cerottini, and P. Romero Induction of Potent Antitumor CTL Responses by Recombinant Vaccinia Encoding a Melan-A Peptide Analogue J. Immunol., January 15, 2000; 164(2): 1125 - 1131. [Abstract] [Full Text] [PDF]
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D. Valmori, J.-F. Fonteneau, S. Valitutti, N. Gervois, R. Dunbar, D. Lienard, D. Rimoldi, V. Cerundolo, F. Jotereau, J.-C. Cerottini, et al. Optimal activation of tumor-reactive T cells by selected antigenic peptide analogues Int. Immunol., December 1, 1999; 11(12): 1971 - 1980. [Abstract] [Full Text] [PDF]
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