Oncolytic potentials of nonhuman viruses for human cancer.III. Infectivity of 3 nonhuman viruses for human cell lines and human tumor mince maintained in vitro

Abstract

This report summarizes our efforts to develop an in vitro test for determining the potential oncolytic activity of specially selected and adapted nonhuman animal viruses. Three of these, bovine enterovirus, BE-1, bovine herpesvirus, IBRV, and simian adenovirus, SV15, were inactivated by debris from either susceptible primary cell cultures or human tumor cell lines, thus demonstrating correlating receptor activity. BE-1 and SV15 receptors in cell debris were heatlabile, but were not adversely affected by trypsin, ether, or EDTA. IBRV receptors were heat and ether sensitive, were not destroyed by trypsin, and were not influenced by EDTA. Following the period of maximal inactivation of BE-1 or SV15 by cell debris, it was found that the virus infectivity could be partially or wholly restored by adjusting the pH of the mixture to approximately 2.0. Attachment studies were performed with minces from 7 human tumors and 4 normal tissues. Although BE-1 and SV15 were inactivated by some of the tumor homogenates, subsequent studies showed that the inactivation was due to heat-stable inhibitors present in the homogenates and, therefore, not specific virus receptors. Virus replication was not demonstrable in tumor or normal tissue minces within the first 24 hours following inoculation; however, after incubation at 36C for 3 to 5 days, several of the inoculated tissues supported virus replication. This conversion from a virus-insensitive to a virussensitive state was presumed to be due to the development of virus receptors during in vitro incubation. It is concluded that such in vitro tests with tumor mince may indicate whether a certain virus will replicate in and possibly destroy the same human tumor in vivo. Negative results of such tests for attachment and replication are probably more meaningful than those of a positive nature.