Immune intervention against virus-associated human cancers.

BACKGROUND: A number of viruses have been shown to be carcinogenic in humans, including Epstein-Barr virus (EBV), hepatitis B virus (HBV), human papillomavirus (HPV) types 16 and 18, and human T-lymphotrophic virus (HTLV) 1. Cancer results from viral transformation of a single progenitor cell; the pathogenesis is complex, and viral infection is only one of many factors involved. Taking EBV-associated tumours as an example, a number of potential immune interventions, aimed at preventing viral infection or targeting virus-positive tumour cells, have been investigated. ENVELOPE GLYCOPROTEIN-BASED VACCINES: The gp340 glycoprotein is the principal target of the neutralizing antibody response to EBV. A vaccine based on purified gp340 has been shown to protect against EBV-associated lymphoproliferative disease (B-cell lymphoma) in an animal model. Phase I clinical trials are being established. CYTOTOXIC T-LYMPHOCYTE(CTL) EPITOPE-BASED VACCINES: EBV infection provokes a powerful CTL-mediated immune response that is directed primarily against the EBNA 3A, 3B, 3C subset of lal viral antigens. Clinical trials are investigating the effect of immunization with synthetic peptides representing EBNA3-derived CTL epitopes. CTL-BASED IMMUNOTHERAPY: Administration of activated T-cells has been shown to reverse lymphoproliferative disease in patients undergoing bone marrow transplantation. This approach may also be useful in other forms of cancer.