Cancer treatment from a common avian virus under study

Researchers on the Blacksburg and College Park, Maryland campuses of the Virginia-Maryland Regional College of Veterinary Medicine have been awarded a major new grant from the National Institutes of Health (NIH) to support innovative work that seeks to develop a treatment for cancer from a common avian virus.

This is the second major grant awarded to Drs. Elankumaran Subbiah of Blacksburg, Va., assistant professor, Department of Biomedical Sciences and Pathobiology (DBSP), and Siba Samal of College Park, Md., associate dean of the college's University of Maryland's campus, for the work which seeks to create a cancer therapy from genetically altered Newcastle disease virus.

According to the American Cancer Society, cancer accounts for nearly one-quarter of all deaths in the United States, exceeded only by heart diseases. It is estimated that 1.4 million new cases of cancer were diagnosed in 2007 alone.

The $430,000 NIH R21 grant will allow Subbiah and Samal to build upon existing work that is focused on the use of reverse genetics to alter NDV to treat prostate cancer.

Reverse genetics (RG) is the process of generating a recombinant virus from cloned complimentary DNA (cDNA) copy, explains Subbiah. Through the RG system, recombinant viruses can be designed to have specific properties that make them attractive as biotechnological tools, live vaccines, and cancer therapies. This is achieved through the introduction of the desired changes in the cDNA, which are then transferred faithfully to the recombinant virus.

“This differs from the previous work in that the recombinant NDV will be targeted against different types of proteases,” said Subbiah. “Different types of cancer cells secrete different types of proteases. We are tailoring the virus to match the type of protease secreted by the cancer cells.”

Normal, healthy cells have an interferon antiviral system that activates upon infection with NDV, thereby preventing replication of the virus, explains Subbiah. Cancer cells, however, have defective interferon antiviral systems, he said. NDV utilizes these defects to replicate specifically in the diseased cells. The replication of NDV generates apoptosis - also known as programmed cell death or cell suicide- in the diseased cell.

According to Subbiah, the use of poultry viruses as cancer therapy poses no threat to humans and several other oncolytic viruses are currently being explored to treat cancer. However, Subbiah's work is the first to alter Newcastle disease virus through a reverse genetic system for selective protease targeting.

Oncolytic virus therapy has gained much attention recently as a result of the progress in understanding virus-host interactions and because currently available chemotherapy is not entirely satisfactory for several reasons, including the possibility of an individual's development of resistance to drugs.

“We are excited about the endless possibilities that Newcastle disease virus offers to treat cancer,” said Subbiah.

Subbiah received his B.V.Sc. in 1984, M.V.Sc. in 1989, and Ph.D. in Veterinary Microbiology in 1996 from the Madras Veterinary College in Madras, India, and was boarded in virology from the American College of Veterinary Microbiologists in 2003. He was a research assistant professor at the VMRCVM's University of Maryland-College Park campus prior to joining Virginia Tech in 2006.

Samal received his B.V.Sc. from Orissa Veterinary College in 1976, his M.V.Sc. from the Indian Veterinary Research Institute, and M.S. and Ph.D. degrees from Texas A&M University. He joined the faculty at the University of Maryland in 1988, and is currently the associate dean of the VMRCVM and chair of the Department of Veterinary Medicine at the University of Maryland, College Park.