At the Albert Einstein College of Medicine of Yeshiva University, US, a team of researchers has been loading radioisotopes onto antibodies as a method of delivering deadly doses of radiation only to virus infected cells.

Using antibodies to deliver a deadly drug or radioisotope is akin to a precision missile locking onto a specific target and then unleashing a toxic payload. While this so-called radioimmunotherapy approach isn't new in cancer treatment, others have used antibodies to target antigens on the surface of tumour cells and thus deliver radioisotopes or deadly drugs to tumours.

For example, Biogen Idec's Zevalin (ibritumomab tiuxetan) is a CD20 targeting monoclonal antibody (MAb) called ibritumomab, combined with a tiucetan, which is a high-affinity, linker-chelator for the radioisotopes Yttrium-90 (Y-90) or Indium-111 (In-111). It is used to treat lymphomas. A second radioimmunotherapy, called Bexxar (iodine131 tositumoma), has been developed by GlaxoSmithKline (GSK) to treat lymphomas.

Instead, Dr Arturo Casadevall and Dr Ekaterina Dadachova's team are targeting viral antigens - proteins expressed by virus-infected cells that can cause those cells to multiply out of control and become cancerous. These are often viewed as inaccessible to antibodies as they typically lurk inside infected cells.

"We had a hunch that rapidly growing tumours can 'outgrow' their blood supply, resulting in dead tumour cells that might spill their viral antigens amongst the living cancer cells," said Dr Casadevall, Associate Professor of Nuclear Medicine and of Microbiology & Immunology at Einstein.

"So we hoped that by injecting antibodies hitched to isotopes into the blood that they'd be carried deep into the tumour mass and would latch onto these now-exposed antigens. Then the blast of radiation emitted by the radioisotope would destroy the live tumour cells nearby."

Nearly 20 per cent of human cancers worldwide are caused by pre-existing virus infections. Prime examples are liver cancer (caused by hepatitis B and C viruses), cervical cancer (caused by human papillomaviruses, HPV) and certain lymphomas (caused by the Epstein-Barr virus).

The Einstein team first concentrated on HPV16-associated cervical cancer to test their theory. They took a MAb that sticks to the viral antigen E6, and attached rhenium-188 particles. They then targeted liver cancer cells with the same radioisotope through the HBx antigen.

Human cancer cell lines were injected into mice followed by the MAbs and in the team discovered that, in both cancers, the radioimmunotherapy resulted in significant slowing of tumour growth compared with tumours in untreated mice. For the cervical-cancer mice, the therapy not only stopped the growth of tumours but even caused them to regress.

"The radioactivity was confined entirely to the tumor masses, leaving healthy tissues undamaged," explained Dr Dadachova, Associate Professor of Nuclear Medicine and of Microbiology & Immunology at Einstein.

"The approach also holds promise for cancer prevention. In people chronically infected with hepatitis B or C, human papillomaviruses, or other viruses known to cause cancer, radioimmunotherapy could potentially eliminate virus-infected cells before they're able to transform into cancer cells," she added.

Not just cancer that can be targeted

Since 2001, Dr Dadachova has also successfully used the technique to target other virus', not associated with cancer, including the major fungal pathogen Cryptococcus neoformans and against a streptococcal bacterium responsible for pneumonia.

Last years, she found that HIV infected cells could be eliminated in vitro and in vivo by targeting gp120 and gp41 viral proteins expressed on the surface of infected cells.

Source: Public Library of Science (PLoS) One

"Treating Cancer as an Infectious Disease - Viral Antigens as Novel Targets for Treatment and Potential Prevention of Tumors of Viral Etiology", Wang et al, 2(10): e1114