Recombinant Poultry Virus Selectively Kills Human Prostate Cancer Cells

A recombinant form of the Newcastle disease virus (NDV) that replicates in humans only in the presence of prostate specific antigen (PSA) was found to kill prostate cancer cells, including hormone resistant cells, without damaging normal tissues.

Newcastle disease is a contagious bird disease affecting many domestic and wild avian species. The virus has a negative-sense, single-stranded genome that codes for a RNA-directed RNA polymerase, hemagglutinin-neuraminidase protein, fusion (F) protein, matrix protein, phosphoprotein, and nucleoprotein in the 5' to 3' direction. Its effects are most notable in domestic poultry due to their high susceptibility and the potential for severe impacts of an epizootic on the poultry industries. Exposure of humans to infected birds can cause mild conjunctivitis and influenza-like symptoms, but NDV otherwise poses no hazard to human health. Interest in the use of NDV as an anticancer agent has arisen from the ability of NDV to selectively kill human tumor cells with limited toxicity to normal cells. However, systemically delivered NDV fails to reach solid tumors in therapeutic concentration and also spreads poorly within the tumors due to barriers including complement, innate immunity, and extracellular matrix.

Investigators at the Virginia Polytechnic Institute (Blacksburg, USA) created a novel recombinant form of NDV in which the F protein was cleavable exclusively by human PSA.

They reported in the January 23, 2013, online edition of the Journal of Virology that the recombinant NDV replicated efficiently and specifically in prostate cancer (CaP) cells and three-dimensional prostaspheres but failed to replicate in the absence of PSA. Furthermore, PSA-cleavable recombinant NDV caused specific lysis of androgen independent and androgen responsive/nonresponsive CaP cells and prostaspheres. PSA-cleavable NDV failed to replicate in chicken embryos, indicating no pathogenicity to chickens.

"Retargeted Newcastle disease virus has major potential advantages over other cancer therapies," said senior author Dr. Subbiah Elankumaran, associate professor of virology at Virginia Polytechnic Institute. "First, its specificity for prostate cancer cells means it would not attack normal cells, thereby avoiding the various unpleasant side effects of conventional chemotherapies. In previous clinical trials, even with extremely large doses of naturally occurring strains, only mild flu-like symptoms were seen in cancer patients. Second, it would provide a new treatment for hormone-refractory patients, without the side effects of testosterone suppression that result from hormonal treatments."

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