Vaccines in breast cancer

Humans usually do not develop potent immune responses against their own cancers. Over the past decade, research in basic immunology has expanded knowledge of antigen processing and the requirements for an effective cancer vaccine. We carried out a study using the viral vaccine ALVAC, a canary pox virus engineered to encode the gene for the tumor-associated antigen carcincoembryonic antigen (CEA), and a T-cell co-stimulatory molecule, B7.1. Sixty-nine patients with CEA-expressing adenocarcinoma were immunized intradermally every other week for 8 weeks. Thirty-nine of these patients were treated with vaccine alone and another 30 patients were administered the same dose in conjunction with granulocyte-macrophage colony-stimulating factor (GM-CSF). Forty-eight hours after vaccination biopsies were obtained from the site of injection. An ELISPOT assay for interferon-γ production was used to assess the induction of CEA-specific T-cell precursors. The therapy was found to be well tolerated. Leukocyte infiltration and CEA expression was observed in the vaccine biopsy sites in all the patients. Six patients with elevated serum CEA values showed a decrease in CEA levels. When reevaluated after the first four vaccines, these patients all had stable disease. About 27% of the patients had stable disease for approximately 5-10 months. The addition of GM-CSF was not associated with improved induction of a CEA-specific T-cell response. It was concluded that in patients with advanced, recurrent adenocarcinomas expressing CEA, ALVAC-CEA B7.1 is a safe vaccine; it is associated with the induction of a CEA-specific T-cell response and can lead to stabilization of disease.