Oncolytic Viral Therapies Require Shielding to Destroy Tumors
(ChemotherapyAdvisor) – Oncolytic reoviruses require a little help from host blood cells in order to evade the host humoral immune response, according to a multinational team of researchers. The conclusion is based on a study entitled “Cell Carriage, Delivery, and Selective Replication of an Oncolytic Virus in Tumor in Patients,” which has been published in the June issue of Science Translational Medicine.
In this study, the investigators aimed to evaluate how oncolytic reoviruses evade the antiviral immune response, as well as how they are preferentially delivered to, and replicated in, tumors over normal tissue. Prior to this study, none of these aspects had been investigated in humans. Colorectal cancer patients were treated with a single cycle of intravenous reovirus prior to previously-planned resection of liver metastases.
Following administration, the reovirus was genome-tracked, being detected in plasma, and blood mononuclear cells, granulocytes, and platelets. “Despite the presence of neutralizing antibodies before viral infusion in all patients, replication-competent reovirus that retained cytotoxicity was recovered from blood cells but not from plasma, suggesting that transport by cells could protect virus for potential delivery to tumors,” the investigators wrote. Malignant cells expressed higher levels of reoviral protein than normal tissue, confirming preferential infection of tumor tissue. Replicating virus was also recovered from tumor tissues but not normal liver.
Based on their findings, the investigators concluded that systemic administration via host cell carriage is necessary to shield a reoviral-based oncolytic vaccine from neutralization by antibodies in vivo, and thus allow for entry into, and destruction of, tumors.