This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Ayyoub, M. Articles by Speiser, D. E. Search for Related Content PubMed PubMed Citation Articles by Ayyoub, M. Articles by Speiser, D. E.

Activation of Human Melanoma Reactive CD8+ T Cells by Vaccination with an Immunogenic Peptide Analog Derived from Melan-A/Melanoma Antigen Recognized by T Cells-1¹

Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, CH-1005 Lausanne [M. A., A. Z., M. J. P., D. V., J-C. C., P. R., D. L., D. E. S.]; Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges [D. R., J-C. C.]; and Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, CH-1005 Lausanne [F. L.], Switzerland

Purpose: As compared with natural tumor peptide sequences, carefully selected analog peptides may be more immunogenic and thus better suited for vaccination. However, T cells in vivo activated by such altered analog peptides may not necessarily be tumor specific because sequence and structure of peptide analogs differ from corresponding natural peptides.

Experimental Design: Three melanoma patients were immunized with a Melan-A peptide analog that binds more strongly to HLA-A*0201 and is more immunogenic than the natural sequence. This peptide was injected together with a saponin-based adjuvant, followed by surgical removal of lymph node(s) draining the site of vaccination.

Results: Ex vivo analysis of vaccine site draining lymph nodes revealed antigen-specific CD8+ T cells, which had differentiated to memory cells. In vitro, these cells showed accelerated proliferation upon peptide stimulation. Nearly all (16 of 17) of Melan-A-specific CD8+ T-cell clones generated from these lymph nodes efficiently killed melanoma cells.

Conclusions: Patient immunization with the analog peptide leads to in vivo activation of T cells that were specific for the natural tumor antigen, demonstrating the usefulness of the analog peptide for melanoma immunotherapy.

This article has been cited by other articles:

				E. B. Walker, W. Miller, D. Haley, K. Floyd, B. Curti, and W. J. Urba Characterization of the Class I-Restricted gp100 Melanoma Peptide-stimulated Primary Immune Response in Tumor-Free Vaccine-draining Lymph Nodes and Peripheral Blood Clin. Cancer Res., April 1, 2009; 15(7): 2541 - 2551. [Abstract] [Full Text] [PDF]

				J. G. Casado, O. DelaRosa, G. Pawelec, E. Peralbo, E. Duran, F. Barahona, R. Solana, and R. Tarazona Correlation of effector function with phenotype and cell division after in vitro differentiation of naive MART-1-specific CD8+ T cells Int. Immunol., January 1, 2009; 21(1): 53 - 62. [Abstract] [Full Text] [PDF]

				E. B. Walker, D. Haley, U. Petrausch, K. Floyd, W. Miller, N. Sanjuan, G. Alvord, B. A. Fox, and W. J. Urba Phenotype and Functional Characterization of Long-term gp100-Specific Memory CD8+ T Cells in Disease-Free Melanoma Patients Before and After Boosting Immunization Clin. Cancer Res., August 15, 2008; 14(16): 5270 - 5283. [Abstract] [Full Text] [PDF]

				D. E. Speiser, P. Baumgaertner, V. Voelter, E. Devevre, C. Barbey, N. Rufer, and P. Romero Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen PNAS, March 11, 2008; 105(10): 3849 - 3854. [Abstract] [Full Text] [PDF]

				L. Chapatte, S. Colombetti, J.-C. Cerottini, and F. Levy Efficient Induction of Tumor Antigen-Specific CD8+ Memory T Cells by Recombinant Lentivectors Cancer Res., January 15, 2006; 66(2): 1155 - 1160. [Abstract] [Full Text] [PDF]

				E. C. Hsueh, E. Famatiga, S. Shu, X. Ye, and D. L. Morton Peripheral Blood CD4+ T-Cell Response Before Postoperative Active Immunotherapy Correlates with Clinical Outcome in Metastatic Melanoma Ann. Surg. Oncol., October 1, 2004; 11(10): 892 - 899. [Abstract] [Full Text] [PDF]

				K. Ida, S. Kawaguchi, Y. Sato, T. Tsukahara, Y. Nabeta, H. Sahara, H. Ikeda, T. Torigoe, S. Ichimiya, K. Kamiguchi, et al. Crisscross CTL Induction by SYT-SSX Junction Peptide and Its HLA-A*2402 Anchor Substitute J. Immunol., July 15, 2004; 173(2): 1436 - 1443. [Abstract] [Full Text] [PDF]