Background
Indoleamine 2,3-dioxygenase (IDO) and survivin have been identified as potential targets for cancer vaccination. In this phase II study a vaccine using the peptides Sur1M2 and IDO5 was combined with the chemotherapy temozolomide (TMZ) for treatment of metastatic melanoma patients. The
Conclusions
These results demonstrate that vaccine-induced immunity towards survivin and IDO-derived peptides can be achieved in combination with TMZ in patients mainly suffering from grade M1c melanoma including patients with brain metastases. A significant clinical activity could not be proven in this small study and a larger setup is needed to properly assess clinical efficacy.
Methods
HLA-A2 positive patients with advanced malignant melanoma were treated biweekly with 150 mg/m2 TMZ daily for 7 days followed by subcutaneous vaccination with 250 µg of each peptide in 500 µL Montanide solution at day 8. Granulocyte-macrophage colony-stimulating factor was used as an adjuvant and topical imiquimod was applied prior to vaccination. Treatment was continued until disease progression. Clinical response was evaluated by PET-CT and immunological outcome was assessed by ELISPOT and flow cytometry.
Results
In total, 17 patients were treated with a clinical benefit rate of 18% including one patient with partial tumor regression. Immune analyses revealed a vaccine specific response in 8 (67%) of 12 patients tested, a significant decrease in the frequency of CD4+ T-cells during treatment, a tendency towards decreasing frequencies of naïve CD4+ and CD8+ T-cells, and increasing frequencies of memory CD4+ and CD8+ T-cells. Conclusions: These results demonstrate that vaccine-induced immunity towards survivin and IDO-derived peptides can be achieved in combination with TMZ in patients mainly suffering from grade M1c melanoma including patients with brain metastases. A significant clinical activity could not be proven in this small study and a larger setup is needed to properly assess clinical efficacy.