ers. In contrast, tumor cell surface expression of CD46, the putative ColoAd1 receptor, appears to increase with stage and grade in a variety of cancers. Thus, ColoAd1 may have therapeutic utility beyond colon cancer, and studies to investigate this are ongoing. Of additional importance are data demonstrating that the seroprevalence of Ad11p is low. Since the greatest need for this type of therapeutic is in patient populations where the tumor has progressed from a confined local disease to a systemic, metastatic cancer, treating patients with an agent to which they do not have pre-existing immunity should enhance the opportunity for the agent to MK 2206 chemical information circulate and eliminate metastatic tumor cells. This is in contrast to Ad5 where seroprevalence, as measured by neutralizing antibodies, reaches levels of approximately 50% in the general population. It is important to note that the potency of ColoAd1 can be complemented by one and potentially more therapeutic transgenes. The ability to arm these agents represents a unique opportunity to impact the treatment of cancer on multiple levels from a single agent. As demonstrated by the incorporation and efficient expression of GFP from the ColoAd1 genome, arming can occur without compromising the potency or selectivity of the viral therapeutic. In addition to incorporating agents that complement the oncolytic potential of the virus, arming creates the opportunity for clinicians to track the activity of the virotherapy treatment in a minimally invasive fashion. This is made all the more meaningful if the method for tracking the virotherapy is 17804601 directly linked to the viral life-cycle. In the case of ColoAd-GFP, this has clearly been demonstrated, where GFP expression was demonstrated to be directly linked to DNA replication. Various genes have been identified that would allow clinicians to track viral activity and include genes associated with 
radionuclide imaging and soluble marker peptides readily detectable in the bloodstream or via urine sampling. Using the expression of the linked gene as a biomarker of viral replication and spread represents an opportunity for clinicians to personalize the treatment, giving additional doses only as needed, thus moving away from standard, timed dosages commonly associated with current chemotherapy treatments. Equally important, as we consider balancing the need for increased potency with safety of the viral therapy, arming could also be used to incorporate a ��safety valve��into the virotherapy, capable of aborting the viralbased therapy through the administration of a clinically approved drug. Importantly, the capacity to arm an oncolytic virus creates an opportunity to build increased potency, safety or enable more personalized medicine, a flexibility unique to this type of anti-cancer agent. Human oncolytic viruses to date have failed in the clinic due to insufficient therapeutic efficacy as monotherapies. To address this, we expanded our search beyond the traditional Ad5 serotype to a series of Ad serotypes representing different viral subgroups. Inviting recombination to increase biodiversity, then applying selective pressure, we developed a unique oncolytic virus, ColoAd1. Deriving oncolytic viruses via tumor selection from A Novel 25730130 Virus for Colon Cancer serotype pools exploits the complex biology of both the viral agent and the tumor. While we demonstrate the principle using adenoviruses, the same approach may be applicable to other viruses and represents a nov
