B2

Purpose: Angiogenesis has been shown to be a critical mechanism for tumor progression. Multiple studies have suggested that tumor growth can be suppressed if tumor angiogenesis can be inhibited using various types of anti-angiogenic agents. We have recently identified VEGFR2-derived epitope peptides restricted to HLA-A*0201 and A*2402 and shown they could be used in the clinical setting. A phase I study was conducted to investigate the safety and immunological response of the vaccination using VEGFR2 peptides.
 Experimental Design: Patients with metastatic cancer received intradermal administrations of VEGFR2 peptide vaccine for four times with one week interval. All patients had advanced disease and received heavy chemotherapy prior to the entry. They have received HLA-A*2402-restricted or HLA-A*0201-restricetd peptide vaccine according to their HLA types. Clinical examination, radiological examination, and blood collection were performed regularly. Immune responses of the PBMC were measured with ELISPOT assay for IFN-γ response and MHC multimer assay for peptide-specific CD8+ T-cells.
 Results: Nine patients have been enrolled in this study. In these patients, six patients have received HLA-A*2402-restricted peptide vaccine, and three patients have received HLA-A*0201-restricetd peptide vaccine. All the enrolled patients have completed the treatment, and five patients received additional doses as the treatment extension. Treatment was well tolerated with no serious adverse events related to the treatment. Significant immune responses were detected as early as 2 week after the 1st injection in some patients. Conclusion: These results suggest that VEGFR2-peptides can be safely administered. In some cases, the vaccination has induced specific immune responses even in the far advanced cancer patients. These results warrant further development of vaccination using VEGFR2 which appears to be an immunogenic antigen.

Second AACR Centennial Conference on Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA