Induction of systemic CTL responses in melanoma patients by dendritic cellvaccination: Cessation of CTL responses is associated with disease progression

Two HLA-A2-positive patients with advanced stage IV melanoma were treated w ith monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE-3 alone or in combination with autolog ous oncolysates. Clinically, the rapid progression of disease was substanti ally stalled and both patients were alive for more than 15 months after ini tiation of therapy. Specific CTL reactivity against several tumor antigens was detectable in peripheral blood, which declined just before reactivation of disease progression. Furthermore, CD3 zeta -chain expression detected b y Western blotting was decreased in PBL at this time. In summary, our data confirm that DC-based vaccinations induce peptide-specific T cells in the p eripheral blood of advanced-stage melanoma patients. Although successful in duction of systemic tumor antigen-specific CTL may not lead to objective cl inical tumor regression, their presence are indicative of a prolonged survi val. (C) 2001 Wiley-Liss, Inc.