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Cancer Viruses

December 2007 - Ground-breaking research from the Albert Einstein College of Medicine of Yeshiva University published in PloS One has demonstrated successful treatment of cancers by targeting causative viruses and raised the possibility of prevention by destroying virus-infected cells before they turn cancerous. Researchers explain that nearly 20 per cent of human cancers result from pre-existing viral infections, for example liver cancer (caused by hepatitis B and C viruses), cervical cancer (caused by human papillomaviruses) and some types of lymphoma (caused by the Epstein-Barr virus).

Senior co-authors Arturo Casadevall and Ekaterina Dadachova together with first author Xing-Guo Wang (visiting scientist from Hubei University, China) and Howard D. Strickler and Robert D. Burk used the technique of radioimmunotherapy which "piggybacks" radioisotopes onto antibodies. Researchers explain that once injected these antibodies target a specific protein and the radioisotope destroys the attached cell. In this study the target was viral antigens; proteins expressed by virus-infected cells that can cause them to become cancerous. Antigens on cell surfaces were known to be susceptible to attack by antibodies but viral antigens associated with cancers typically remain inside infected cells, and were assumed to be out of reach.

Dr. Arturo Casadevall, Forchheimer Professor and chair of microbiology & immunology said:

"We had a hunch that rapidly growing tumors can 'outgrow' their blood supply, resulting in dead tumor cells that might spill their viral antigens amongst the living cancer cells. So we hoped that by injecting antibodies hitched to isotopes into the blood that they'd be carried deep into the tumor mass and would latch onto these now-exposed antigens. Then the blast of radiation emitted by the radioisotope would destroy the live tumor cells nearby."

Testing their theory in mice, researchers attached the radioisotope rhenium-18 to monoclonal antibodies made against viral antigens E6 (expressed by almost all cervical-cancer cells) and HBx (made by liver-cancer cells). In both cases, radioimmunotherapy resulted in significant reduction in tumor growth compared with tumors in untreated mice. In mice with cervical cancer, the therapy also caused tumor regression.

Dr. Ekaterina Dadachova, associate professor of nuclear medicine and of microbiology & immunology commented:

"Radioimmunotherapy not only worked against these cancers, but in addition the radioactivity was confined entirely to the tumor masses, leaving healthy tissues undamaged."

In a series of animal studies beginning in 2001, Dr. Dadachova has pioneered successful applications of radioimmunotherapy in the treatment of infection-related diseases such as the fungal pathogen Cryptococcus neoformans and a streptococcal bacterium responsible for pneumonia. In 2006, she and her colleagues showed that this technique could help halt HIV by targeting one of several viral proteins displayed on the surface of infected cells.

Ekaterina Dadachova added:

"Virus-associated cancers account for some 1.3 million cancer cases each year, so the need for new strategies in treating them is obvious and urgent. Our study has shown in principle that radioimmunotherapy can help in treating cancers caused by viruses - and, just as exciting, 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."

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