Abstract Prophylactic vaccines have been a major advance in preventing the development of infections after exposure to pathogens. When contemplating an effective approach to cancer prevention, vaccines offer unique advantages over other more standard approaches: First, once appropriately stimulated, antigen-specific T cells will travel to all sites of disease and eradicate cells bearing the proteins to which the T cells have been primed by vaccination. Second, successful immunization will further result in the development of immunologic memory, providing lifelong immunologic surveillance. There is evidence of an adaptive tumor immune infiltrate even at the earliest stages of breast and colon cancer development. Furthermore, there is measurable immunity to lesion-associated antigens present in patients who will eventually develop malignancy even before cancer is clinically evident. Recent studies are beginning to unmask the preinvasive antigenic repertoire for these two malignancies. Preliminary experiments in transgenic mouse models of mammary and intestinal tumors suggest that immunization against antigens expressed in preinvasive and high-risk lesions may be effective in preventing the development of invasive malignancy. Introduction Prophylactic vaccines that target pathogens, which cause significant human morbidity and mortality, has been one of the most successful interventions used in humans to prevent disease. In the United States alone, there has been a 99% decrease in the incidence of infectious diseases that are targeted by common childhood vaccinations (1). The success of vaccines in the prevention of infectious disease has resulted in exploring immune-targeting approaches for the prevention and/or treatment of a variety of non-infectious diseases, such as Alzheimer disease, atherosclerosis, cancer, and even nicotine addiction (2-4). To be effective, vaccines must arm the immune system to destroy the cause of disease. In an infection, the pathogen has been defined, but in malignancy the initiating abnormality is generally unknown. Although the specific cause of a cancer may be mul-tifactorial, there are a limited number of genetic alterations that will stimulate the initiation and maintenance of the malignancy. If we could define the antigenic repertoire of preinvasive high-risk lesions, perhaps the immune system could be armed via vaccination to eradicate cells expressing those proteins to prevent the development of cancer.
展开▼
