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 Tatsumi, T. Articles by Storkus, W. J. Search for Related Content PubMed PubMed Citation Articles by Tatsumi, T. Articles by Storkus, W. J.

MAGE-6 Encodes HLA-DRß1*0401-presented Epitopes Recognized by CD4+ T Cells from Patients with Melanoma or Renal Cell Carcinoma¹

Departments of Surgery [T. T., L. S. K., E. R., Y. L. K., W. J. S.], Medicine [J. M. K.], and Immunology [W. J. S.], University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; Department of Emergency and Organ Transplantation, Section of Nephrology, University of Bari, Bari, Italy [E. R., L. G., F. P. S.]; Cleveland Clinic Foundation, Cleveland, Ohio 44195 [J. H. F., R. M. B.]; Kent Ridge Digital Laboratory, Singapore, [V. B.]; Epimmune Corporation, San Diego, California 92121 [J. S., A. S.]; Department of Medicine, Indiana University, Indianapolis, Indiana 46202 [T. F. L.]; Department of Surgery, University of Virginia, Charlottesville, Virginia 22908 [C. L. S.]; and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15261 [J. M. K., W. J. S.]

CD4+ T cells modulate the magnitude and durability of CTL responses in vivo and may serve as potent effector cells within the tumor microenvironment. The current study was undertaken to define novel epitopes from the broadly expressed tumor antigen MAGE-6 that are recognized by CD4+ T cells. We have combined the use of a HLA-DR4/peptide binding algorithm with the IFN- enzyme-linked immunospot assay to identify four nonoverlapping sequences derived from the MAGE-6 protein that served as CD4+ T-cell epitopes in HLA-DR4+ donors. Strikingly, patients with active melanoma or renal cell carcinoma failed to secrete IFN- in response to MAGE-6-derived epitopes, whereas both normal donors and cancer patients with no current evidence of disease were responsive, particularly after short-term in vitro stimulations with peptide-pulsed dendritic cells. Importantly, peptide-specific CD4+ T cells also recognized HLA-DRß1*0401+ tumor cells that constitutively expressed the MAGE-6 protein and autologous HLA-DRß1*0401+ dendritic cells transfected with MAGE-6 cDNA-elicited CD4+ T cells that reacted against individual peptide epitopes in vitro. These data suggest that MAGE-6-derived epitopes could serve as useful vaccine candidate components and may provide an immune-monitoring index of clinically important Th1-type immunity in patients with renal cell carcinoma or melanoma.

This article has been cited by other articles:

				T. Das, G. Sa, C. Hilston, D. Kudo, P. Rayman, K. Biswas, L. Molto, R. Bukowski, B. Rini, J. H. Finke, et al. GM1 and Tumor Necrosis Factor-{alpha}, Overexpressed in Renal Cell Carcinoma, Synergize to Induce T-Cell Apoptosis Cancer Res., March 15, 2008; 68(6): 2014 - 2023. [Abstract] [Full Text] [PDF]

				L. Vujanovic, M. Mandic, W. C. Olson, J. M. Kirkwood, and W. J. Storkus A Mycoplasma Peptide Elicits Heteroclitic CD4+ T Cell Responses against Tumor Antigen MAGE-A6 Clin. Cancer Res., November 15, 2007; 13(22): 6796 - 6806. [Abstract] [Full Text] [PDF]

				J. M. Kirkwood Building Upon the Standard of Care in Adjuvant Therapy of High-Risk Melanoma J. Clin. Oncol., December 1, 2005; 23(34): 8559 - 8563. [Full Text] [PDF]

				D. A. Hokey, A. T. Larregina, G. Erdos, S. C. Watkins, and L. D. Falo Jr. Tumor Cell Loaded Type-1 Polarized Dendritic Cells Induce Th1-Mediated Tumor Immunity Cancer Res., November 1, 2005; 65(21): 10059 - 10067. [Abstract] [Full Text] [PDF]

				A. Paschen, M. Song, W. Osen, X. D. Nguyen, J. Mueller-Berghaus, D. Fink, N. Daniel, M. Donzeau, W. Nagel, H. Kropshofer, et al. Detection of Spontaneous CD4+ T-Cell Responses in Melanoma Patients against a Tyrosinase-Related Protein-2-Derived Epitope Identified in HLA-DRB1*0301 Transgenic Mice Clin. Cancer Res., July 15, 2005; 11(14): 5241 - 5247. [Abstract] [Full Text] [PDF]

				P. Rayman, A. K. Wesa, A. L. Richmond, T. Das, K. Biswas, G. Raval, W. J. Storkus, C. Tannenbaum, A. Novick, R. Bukowski, et al. Effect of Renal Cell Carcinomas on the Development of Type 1 T-Cell Responses Clin. Cancer Res., September 15, 2004; 10(18): 6360S - 6366S. [Abstract] [Full Text] [PDF]

				J. Lin, L. Lin, D. G. Thomas, J. K. Greenson, T. J. Giordano, G. S. Robinson, R. A. Barve, F. A. Weishaar, J. M. G. Taylor, M. B. Orringer, et al. Melanoma-Associated Antigens in Esophageal Adenocarcinoma: Identification of Novel MAGE-A10 Splice Variants Clin. Cancer Res., September 1, 2004; 10(17): 5708 - 5716. [Abstract] [Full Text] [PDF]

				H. L. Hanson, S. S. Kang, L. A. Norian, K. Matsui, L. A. O'Mara, and P. M. Allen CD4-Directed Peptide Vaccination Augments an Antitumor Response, but Efficacy Is Limited by the Number of CD8+ T Cell Precursors J. Immunol., April 1, 2004; 172(7): 4215 - 4224. [Abstract] [Full Text] [PDF]