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

Abstract

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.