Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: cessation of CTL responses is associated with disease progression.

Two HLA-A2-positive patients with advanced stage IV melanoma were treated with monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE-3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease was substantially stalled and both patients were alive for more than 15 months after initiation 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 by Western lotting was decreased in PBL at this time. In summary, our data confirm that DC-based vaccinations induce peptide-specific T cells in the peripheral blood of advanced-stage melanoma patients. Although successful induction of systemic tumor antigen-specific CTL may not lead to objective clinical tumor regression, their presence are indicative of a prolonged survival.