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Durable clinical responses in patients with metastatic melanoma vaccinated with dendritic cells loaded with killed allogeneic melanoma cells.

2576 Background: We demonstrated that DCs loaded with killed allogeneic tumors can cross-prime tumor-specific naïve CD8+T cells in vitro. Clinically this approach would overcome HLA restriction inherent to peptide vaccines and allow diversification of immune responses including priming of many clones of CD8+ and CD4+ T cells.


METHODS
Twenty (20) patients with metastatic melanoma were vaccinated with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line. A total of 8 vaccines were administered at monthly intervals. DCs were generated from monocytes by culturing with GM-CSF and IL-4 and activated by additional culture with TNFα and CD40 ligand. KLH was used as a control antigen. The first patient was accrued December, 2002 and the last November, 2003.


RESULTS
DC vaccinations induced durable objective clinical responses in two patients who had progressive metastatic disease after previous cytotoxic chemotherapy. One patient experienced a CR and one patient a PR both remissions have lasted ≥ 20 months. Fourteen patients were alive at 12 months and 9 patients are alive at the end of 2005. The estimated median overall survival is 22 months with a range of 2-31 months. DC vaccination led to elicitation of CD8+T cell immunity specific to MART-1 tissue differentiation antigen, suggesting that cross-priming/presentation of melanoma antigens by the DC vaccines had occurred in vivo. Vaccinations were safe and tolerable. There were no significant adverse events.


CONCLUSIONS
The present results justify the design of larger follow-up studies to assess the immunological and clinical response to DC vaccines in patients with metastatic melanoma and other malignant diseases. No significant financial relationships to disclose.