BIIR scientists have built a clinical program based on utilizing dendritic cells as novel therapeutic vaccines in cancer. Initial trials were conducted in patients with metastatic melanoma. These trials brought the proof of principle that dendritic cell vaccines are safe, can activate the immune system against cancer, and are of potential therapeutic value. Several clinical studies have been completed and are ongoing.

Our first clinical study was performed with a: CD34-DC vaccine pulsed with several melanoma peptides. The CD34-DC vaccine is composed of three distinct subsets, which are generated by culturing CD34+ hematopoietic progenitors. DCs are pulsed with the helper antigen Keyhole Limpet Hemocyanin (KLH) and with peptides derived from 4 melanoma antigens (MelanA/MART-1, tyrosinase, MAGE-3 and gp100). In this clinical study, 18 consecutive HLA-A201 patients with metastatic melanoma received 4 DC vaccines (induction phase) and 12 of these patients received additional vaccines, consolidation phase. As the trial was initiated in March 1999, we now have a long-term follow-up (>30 months for 6 patients and up to 52 months). The analysis of immune responses in the blood and of clinical responses allowed us to draw several important conclusions.

• Vaccination with Dendritic Cells is remarkably safe.
• Some patients developed tumor specific T cell immunity in response to DC vaccinations.
• Some patients with metastatic melanoma have developed partial and complete clinical responses following vaccination.
• Patients who did not develop tumor specific immunity did not show clinical regression.

Yet a number of limitations are associated with the above vaccine, for example restriction to a certain HLA type. Therefore, a novel vaccine has been developed at BIIR where DCs are generated from monocytes and are loaded with killed allogeneic melanoma cell line. This has three important advantages: it permits to activate many types of patients' T cells against cancer, it permits us to treat patients regardless of their white blood cell type (HLA antigens), and it permits us to treat cancers for which no tumor antigens have been identified yet. An early assessment suggests that this vaccine is safe and may be capable of inducing regression of metastatic lesions.