Epitope spreading occurs in cancer patients after vaccination with a single tumor antigen

Abstract

Vaccination of cancer patients using dendritic cells (DC) was shown to be effective for B cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DC pulsed with HER-2/neu or MUC1 derived peptides. Ten patients were included in this pilot study. The DC vaccinations were well tolerated with no side effects. One patient developed a complete regression of her multiple subcutaneous lesions. In 5 out of 10 patients, antigen specific cytotoxic T-cells (CTL) could be detected in the peripheral blood using both intracellular IFN-γ staining and 51Cr-release assays. The major CTL response in vivo was induced with the HER-2/neu derived E75 and the MUC1 derived M1.2 peptide which lasted for more than 6 months, suggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1 peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1 specific T-cells were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Our results show that vaccination of DC pulsed with a single tumor antigen may induce immunological and clinical responses in breast and ovarian cancer. This study may be relevant to the design of future clinical trials of other peptide-based cancer vaccines.