Viral Agents Oncolytic for Human Tumors in Heterologous Host. Oncolytic Effect of Coxsackie B Viruses.

Abstract

1. The Toolan technic for growing cancer tissue in a heterologous host was applied to growth of tissue culture propagated HeLa and KB cells in the peritoneal cavity of rat. This method resulted in rapid development of large healthy explants of carcinoma on peritoneal surfaces, particularly of omentum. Ninety-three% of rats inoculated developed comparatively uniform tumor masses, thus allowing for adequately controlled studies of virus growth and oncolytic effects. 2. A preliminary survey of adenovirus, ECHO, and Coxsackie agents in rat-HeLa tumor system produced 3 types of reaction: 1. failure of some agents to grow. 2. growth of virus without oncolytic activity, and, 3. growth of virus with evidence of slight or incomplete oncolytic effects. Four Coxsackie agents, types B₁, B₂, B₃, and B₅, showed initial evidence of growth, and on serial passage through rat-HeLa tumors, increased capacity for destroying solid carcinoimata in vivo, producing characteristic histological changes. The oncolytic Coxsackie B₃ virus produced by rat-HeLa tumor passage in vivo, compared to the same strain passed in HeLa cells grown in tissue culture, revealed marked differences in oncolytic capacity. Use of this method illustrates the possibility of virus adaptation by tumor to tumor passage; that this principle has been successfully employed to destroy solid tumor transplants of human origin, suggests its possible application for future clinical studies.