Targeting the Virus with Radioimmunotherapy in Virus-Associated Cancers

Abstract

"Virus-associated cancer" (VAC) refers to a cancer where viral infection results in the malignant transformation of the host's infected cells. Examples of viruses linked to cancers are the Epstein-Barr virus (EBV), which is associated with lymphomas, as well as nasopharyngeal and breast cancer; hepatitis B virus (HBV) and hepatitis C virus (HCV), which are both associated with hepatocellular carcinoma; and human papilloma viruses (HPVs), which are associated with cancer of the cervix. We have recently demonstrated that HIV-1-infected cells can be eliminated in vitro and in vivo by targeting viral glycoproteins expressed on the surface of infected cells with radiolabeled viral protein-specific monoclonal antibodies and proposed that this approach can be applicable to the broad range of viral infectious diseases. In VAC, the tumor cells can exhibit viral antigens both internally or on their surfaces. As a result, viral antigens in tumors represent a potential antigenic target that is clearly different from normal tissues. In principle, these proteins could be targeted by radioimmunotherapy (RIT). In this paper, we describe the potential of this approach and review some of the issues involved in the development of this approach. RIT of VAC is fundamentally different from the previously described uses of RIT, which have targeted tumor-associated antigens that are "self" proteins.