Prospects for Prevention and Treatment

Vaccination Is Not Immunization Vaccine Risks Exposed

Vaccines Have Serious Side Effects

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The identification of a human tumor virus immediately suggests strategies for tumor prevention and control. Public heath measures can be instituted to protect the population from exposure or to identify carriers or people at elevated risk of cancer. Successful examples of this approach are the elimination of HBV and HCV from the blood supply and the use of Pap screening to identify women with HPV-induced cervical dysplasia. In a more recent example, maternal-to-infant transmission of HTLV-1 is reduced if carrier mothers refrain from breast-feeding (Hino et al., 1997). Another well-established modality to control viral infection is vaccination. An effective hepatitis B vaccine is already reducing the incidence of chronic hepatitis B virus infection and hepatocellular carcinoma (Huang and Lin, 2000), and on the basis of clinical trials demonstrating protection against persistent high-risk HPV infection and the development of precancerous lesions, HPV vaccines were recently approved for distribution (Koutsky et al., 2002; Harper et al., 2004; Villa et al., 2005). Vaccines such as these that are targeted at virus particles or structural proteins are referred to as prophylactic vaccines andrely on the production of neutralizing antibodies that prevent viral infection. These vaccines are expected to be of greatest benefit to people who have not yet been exposed to the targeted virus. Prophylactic vaccines may also be used in infected people to reduce the titer of infectious virus in tissues and body fluids, the number of infected cells, or the concentration of viral gene products in infected cells. Such effects may well reduce the likelihood of malignant progression or transmission of the virus to a new host. Antiviral drugs that interfere with virus replication may provide similar benefits. However, prophylactic vaccines are unlikely to be beneficial to patients who already have precancerous changes or cancer itself. For such people, therapeutic vaccines are being developed that induce the generation of cytotoxic T lymphocytes that recognize and kill tumor cells that express viral proteins (Schreckenberger and Kaufmann, 2004). Since the expression of many cellular genes is under the control of viral proteins in cancer cells, some cellular proteins that are induced by the virus may also serve as tumor rejection antigens.

Tumor virus genomes and proteins in the cancer cells are also well-defined therapeutic targets. It may be possible to use antiviral agents that inhibit the replication or expression of viral genomes in cancer cells or that interfere with function of viral proteins required for cancer cell survival or growth. Such agents might include RNAi, micro RNA, ribozymes, or other nucleases that directly bind to and degrade viral DNA or RNA, as well as small molecules that interfere with expression or activity of viral proteins. These approaches are expected to be useful in virally induced cancers that continuously require viral gene products for proliferation or survival. Because viral genes and gene products are present in infected cells only, it may be possible to develop highly specific antiviral drugs that prevent or inhibit cancer growth with minimal effects on normal uninfected tissue.

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