Abstract
BackgroundNearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples being hepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers.Methodology/Principal FindingsViral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC) and Hepatitis B-associated hepatocellular carcinoma (HCC) by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with 188Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies.Conclusions/SignificanceThis strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer.
Highlights
It has been estimated that nearly 20% of human cancers worldwide have an infectious etiology [1]
Most of these tumors are of viral origin, and include firmly established associations of hepatitis B virus (HBV) and hepatitis C virus (HCV) with hepatocellular carcinoma; and of human papillomavirus (HPV)-with cancers of the cervix, anus, vulva, vagina; as well as associations of oropharynx EpsteinBarr virus (EBV) with lymphoma and nasopharyngeal carcinoma; human T lymphotropic virus type 1 (HTLV-1)-with adult T-cell leukemia/lymphoma, and human herpes virus 8 (HHV-8)-with Kaposi sarcoma [2,3,4,5,6,7]
These virus-associated tumors represent a burden of approximately 1.3 million cases of cancer each year, with HBV/HCV-associated liver cancer accounting for 523,000 cases, and HPV-associated tumors accounting for 561,000 cases [8]
Summary
It has been estimated that nearly 20% of human cancers worldwide have an infectious etiology [1] Most of these tumors are of viral origin, and include firmly established associations of hepatitis B virus (HBV) and hepatitis C virus (HCV) with hepatocellular carcinoma; and of human papillomavirus (HPV)-with cancers of the cervix, anus, vulva, vagina; as well as associations of oropharynx EpsteinBarr virus (EBV) with lymphoma and nasopharyngeal carcinoma; human T lymphotropic virus type 1 (HTLV-1)-with adult T-cell leukemia/lymphoma, and human herpes virus 8 (HHV-8)-with Kaposi sarcoma [2,3,4,5,6,7]. It raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer
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