Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells

PURPOSE Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c+ myeloid DCs, naturally circulating in the blood. EXPERIMENTAL DESIGN Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous CD1c+ myeloid DCs, activated by only brief (16h) ex vivo culture and loaded with tumor associated antigens of tyrosinase and gp100. RESULTS Our results show that therapeutic vaccination against melanoma with small amounts (3-10x106) of myeloid DCs is feasible and without substantial toxicity. Four out of fourteen patients showed long-term progression-free survival (12-35 months), which directly correlated with the development of multifunctional CD8+ T cell responses in three of these patients. In particular, high CD107a expression, indicative for cytolytic activity, and IFN as well as tumor necrosis factor (TNF)α and CCL4 production was observed. Apparently, these T cell responses are essential to induce tumor regression and promote long-term survival by stalling tumor growth. CONCLUSION We show that vaccination of metastatic melanoma patients with primary myeloid DCs is feasible and safe and results in induction of effective anti-tumor immune responses that coincide with improved progression-free survival.

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