PT - JOURNAL ARTICLE AU - Rosenberg, Steven A. AU - Sherry, Richard M. AU - Morton, Kathleen E. AU - Scharfman, William J. AU - Yang, James C. AU - Topalian, Suzanne L. AU - Royal, Richard E. AU - Kammula, Udai AU - Restifo, Nicholas P. AU - Hughes, Marybeth S. AU - Schwartzentruber, Douglas AU - Berman, David M. AU - Schwarz, Susan L. AU - Ngo, Lien T. AU - Mavroukakis, Sharon A. AU - White, Donald E. AU - Steinberg, Seth M. TI - Tumor Progression Can Occur despite the Induction of Very High Levels of Self/Tumor Antigen-Specific CD8<sup>+</sup> T Cells in Patients with Melanoma AID - 10.4049/jimmunol.175.9.6169 DP - 2005 Nov 01 TA - The Journal of Immunology PG - 6169--6176 VI - 175 IP - 9 4099 - http://www.jimmunol.org/content/175/9/6169.short 4100 - http://www.jimmunol.org/content/175/9/6169.full SO - J. Immunol.2005 Nov 01; 175 AB - The identification of many tumor-associated epitopes as nonmutated “self” Ags led to the hypothesis that the induction of large numbers of self/tumor Ag-specific T cells would be prevented because of central and peripheral tolerance. We report in this study on vaccination efforts in 95 HLA-A*0201 patients at high risk for recurrence of malignant melanoma who received prolonged immunization with the “anchor-modified” synthetic peptide, gp100209–217(210M). Vaccination using this altered peptide immunogen was highly effective at inducing large numbers of self/tumor-Ag reactive T cells in virtually every patient tested, with levels as high as 42% of all CD8+ T cells assessed by tetramer analysis. From 1 to 10% of all CD8+ cells were tumor-Ag reactive in 44% of patients and levels &gt;10% were generated in 17% of patients. These studies were substantiated using the ELISPOT assay and a bulk cytokine release assay. Although our data regarding “tumor escape” were inconclusive, some patients had growing tumors that expressed Ag and HLA-A*0201 in the presence of high levels of antitumor T cells. There was no difference in the levels of antitumor Ag-specific T cells in patients who recurred compared with those that remained disease-free. Thus, the mere presence of profoundly expanded numbers of vaccine-induced, self/tumor Ag-specific T cells cannot by themselves be used as a “surrogate marker” for vaccine efficacy. Further, the induction of even high levels of antitumor T cells may be insufficient to alter tumor progression.