Biodistribution of Oncolytic Measles Virus After Intraperitoneal Administration into Ifnar™-CD46Ge Transgenic Mice

Abstract

In support of a proposed phase I clinical trial, we studied the biodistribution of virus-infected cells after intraperitoneal administration of oncolytic measles viruses to alpha/beta interferon-defective mice expressing human CD46 with human-like tissue specificity. Various marker genes were employed, and green fluorescent protein proved to be most informative. Mesothelium and ovarian surface epithelium were remarkably resistant to infection, but infected peritoneal macrophages were present in abundance both in peritoneal lavage fluid and in the greater omentum, where they were heavily concentrated in "milky spots". Infected macrophages were also identified outside the peritoneal cavity, along the peritoneal fluid drainage pathway and in the spleen. Thus, diaphragmatic stomata, thoracic lymphatic vessels, and parathymic lymph nodes contained numerous measles-infected cells, as did the marginal zones of the white pulp of the spleen. Splenic marginal zone macrophages were the predominant targets of infection after intravenous administration of oncolytic measles viruses. When measles-infected peritoneal macrophages were adoptively transferred, they did not migrate beyond the confines of the peritoneal cavity, suggesting that, after intraperitoneal virus administration, the positive cells in thoracic lymphatics, parathymic lymph nodes, and spleen are nonmigratory cells transduced in situ by viral particles that have exited from the peritoneal cavity.