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peptide vaccine prevents her2 tumors in mice, even stopped advanced tumors progressng
Peptide Vaccine Prevents Spontaneous Tumor Formation in Mice
NEW YORK (Reuters Health) Feb 26 - In a mouse model of spontaneous breast cancer, a peptide vaccine prevented tumor formation, investigators report in the February 1st issue of Cancer Research. The vaccine slowed or stopped their progression even if the vaccine was administered after tumors reached an advanced stage.
Previous work with antigen-binding peptides derived from tumor-associated antigens suggested that they could be used to treat common cancers, Dr. Esteban Celis, from the University of South Florida in Tampa, and his associates note. However, progress was stymied in the laboratory because of the artificiality of the models being used, such as foreign proteins used to generate the peptides and transplanted tumor cell-lines.
They suggest that progress will accelerate now that more physiological cancer models are available. In their current study, they used transgenic female BALB/neuT mice that carry the activated rat HER-2/neu oncogene. These mice express HER1/neu in the breast at about 6 weeks of age, and develop multiple spontaneous tumors at 15 to 20 weeks.
To demonstrate the feasibility of using peptide vaccines, Dr. Celis and his team first generated multiple candidate synthetic peptide vaccines corresponding to a cytotoxic T lymphocyte epitope from the HER-2/neu antigen. The "p66" peptide was identified as being the most effective in eliciting tumor-reactive cytotoxic T lymphocytes in control mice.
When tested in BALB/neuT mice, administration of p66 along with the immunostimulatory agent CpG induced anti-tumor activity. However, extended protection required either removal of CD4/CD25 regulatory T cells or multiple booster vaccinations. When the authors treated the animals with anti-CD25 monoclonal antibody, the vaccination increased the tumor-specific response about 5-fold.
When mice were vaccinated with p66+CpG and subsequently challenged with cultured cells isolated from a BALB/neuT mouse, the animals were significantly protected. However, numbers of tumor-reactive cytotoxic T lymphocyte responses were increased when the animals were pretreated with anti-CD25 monoclonal antibody. By the end of the experiment on day 125, three of five mice treated in this manner remained tumor-free.
When cancer cells were implanted prior to vaccination, the tumors' growth was slowed, but not stopped. If pretreated with anti-CD25, the tumors ceased to grow altogether. After vaccinating the animals two more times, the mice survived.
The scientists also found that the treatments also provided a prophylactic effect against spontaneous mammary tumors.
Dr. Celis and his associates conclude that "a strong case has been made to preferentially use cancer vaccines in the prophylactic setting, or in a relatively disease-free condition that could be achieved by early detection, or post-surgery, radiation, or chemotherapy."
Cancer Res 2007;67:1326-1334.
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