The vaccinia virus is a large enveloped virus that contains a double stranded DNA genome and belongs to the poxvirus family. It is famous for its role in the worldwide program lead by the World Health Organization to eradicate smallpox. Vaccinia virus was used to develop a vaccine against smallpox, which eventually lead to the complete elimination of the disease from human populations. In fact, the term vaccination is derived from the vaccinia virus name because of the origin of the first cowpox vaccine by Dr. Edward Jenner. Recently, scientists have found a new use for the vaccinia virus. Medical researchers have always hypothesized that if cancer cells were able to be specifically targeted by anticancer treatment that the effects of the treatments could be amplified and more specific. Scientists have now engineered the vaccinia virus to specifically target cancer cells. The results of the research were published online in the journal Nature. The vaccinia virus was engineered to specifically target cancer cells that harbor the activation of a particular oncogenic pathway known as the epidermal growth factor receptor (EGFR)/ Ras pathway. This pathway is activated and amplified in several types of cancer cells. The newly engineered vaccinia virus has been termed JX-594 and is designated as an oncolytic poxvirus. These initial studies were designed to study the safety of the virus, and are still preliminary but have shown promising results. The investigators injected 23 patients with metastatic cancer with several dose concentrations of JX-594. In the patients that received the highest doses of the engineered vaccinia virus, seven out of eight had the virus specifically targeted to their tumors but not their healthy tissue. The researchers envision the engineered virus being able to efficiently deliver biological molecules such as peptides and small interfering RNAs to cancer cells while sparing normal tissues. The authors wrote, “Here we report the first reproducible dose related delivery, replication and transgene expression from a viral vector or oncolytic virus in metastatic solid tumours in humans after intravenous administration. Engineered oncolytic poxviruses such as JX-594 can express several complementary therapeutic proteins and/or siRNAs in metastatic tumours systemically and in a cancer-selective fashion; therapeutic concentrations in tumour tissues should therefore be markedly higher than in normal tissues”. Future studies will focus on the delivery of specific cancer treatment molecules to the targeted cancer cells. Although this technology is in its infancy, the potential is great and could eventually lead to the development of tissue specific and targeted cancer treatments.
Caroline J. Breitbach et al. “Intravenous delivery of a multimechanistic cancer-targeted oncolytic poxvirus in humans” Nature published online August 31, 2011 doi:10.1038/nature10358