Abstract
<div>Abstract<p><b>Purpose:</b> Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) has multiple advantages compared to peptide loading. We investigated the immunologic and clinical responses to vaccination with mRNA-electroporated DC in stage III and IV melanoma patients.</p><p><b>Experimental design:</b> Twenty-six stage III HLA*02:01 melanoma patients scheduled for radical lymph node dissection (stage III) and 19 melanoma patients with irresectable locoregional or distant metastatic disease (referred to as stage IV) were included. Monocyte-derived DC, electroporated with mRNA encoding gp100 and tyrosinase, were pulsed with keyhole limpet hemocyanin and administered intranodally. TAA-specific T-cell responses were monitored in blood and skin-test infiltrating lymphocyte (SKIL) cultures.</p><p><b>Results:</b> Comparable numbers of vaccine-induced CD8<sup>+</sup> and/or CD4<sup>+</sup> TAA-specific T-cell responses were detected in SKIL cultures; 17/26 stage III patients and 11/19 stage IV patients. Strikingly, in this population, TAA-specific CD8<sup>+</sup> T cells that recognize multiple epitopes and produce elevated levels of IFNγ upon antigenic challenge <i>in vitro</i>, were significantly more often observed in stage III patients; 15/17 versus 3/11 stage IV patients, <i>P</i> = 0.0033. In stage IV patients, one mixed and one partial response were documented. The presence or absence of IFNγ-producing TAA-specific CD8<sup>+</sup> T cells in stage IV patients was associated with marked difference in median overall survival of 24.1 months versus 11.0 months, respectively.</p><p><b>Conclusion:</b> Vaccination with mRNA-electroporated DC induces a broad repertoire of IFNγ producing TAA-specific CD8<sup>+</sup> and CD4<sup>+</sup> T-cell responses, particularly in stage III melanoma patients. <i>Clin Cancer Res; 18(19); 5460–70. ©2012 AACR</i>.</p></div>
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