Oncolytic Potentials of Nonhuman Viruses for Human Cancer. I. Effects of Twenty-Four Viruses on Human Cancer Cell Lines

Summary

An attempt was made to select from animal viruses, believed nonpathogenic for man, those which could be adapted to produced cytopathic effect (CPE) in malignant human cell lines. It was hoped that certain of these might prove oncolytic in vivo without risk to the patient and that antibody development might be poor or delayed under such circumstances. Twenty-four viruses were screened for oncolytic potential in HeLa, HEp-2, KB, HAd-1, and HEp-3 cell lines. They were classified as cytopathic (producing CPE and multiplying, grades + to + + + +), infective, probably infective, and not infective. Nine feline, 4 swine, and 2 simian viruses were eliminated after being placed in the last category. Nine viruses, including 4 simian adenoviruses (S.V.₁, S.V.₁₅, S.V.₃₃, and S.V.₃₄), 4 bovine (BE-1, BE-180, IBR, and BVV), and 1 equine virus (ERP), grew or were “adapted” to multiply well on at least one cell line. S.V.₁, S.V.₃₃, and S.V.₃₄, though multiplying well, were not adapted to effect good CPE. Fourteen virus-cell line combinations of the 6 best viruses were serially passed from 5 to 35 times and produced + + + + CPE and titers ranging from 10^4.5 to 10^7.3 per ml. Sometimes adaptation to one cell line resulted in adaptation to several others. Final candidates among the 24 viruses were S.V.₁₅, a simian adenovirus, BE-1, BE-180, and BVV, probable bovine enteroviruses, and IBR and ERP, bovine and equine herpes viruses, respectively. Attempts were made to collect further evidence that these viruses were not originally infective for man and did not lead to inapparent infection in the workers handling them for a long period in the laboratory. Selected human gamma globulin pools, small human serum pools, and repeated sera from laboratory personnel were interpreted as negative by neutralization test, except for one small serum pool of unidentified blood donors against one agent. These 6 viruses are now being serially passed in and tested for oncolytic activity in a series of hetertransplanted human tumors, and concentrated pools are being prepared for therapeutic tests in man.