Safety and biodistribution of a double-deleted oncolytic vaccinia virus encoding CD40 ligand in laboratory Beagles.
We evaluated adverse events, biodistribution and shedding of oncolytic vaccinia virus encoding CD40 ligand in two Beagles, in preparation for a phase 1 trial in canine cancer patients. Dog 1 received one dose of vaccinia virus and was euthanized 24 hours afterwards, while dog 2 received virus four times once weekly and was euthanized 7 days after that. Dogs were monitored for adverse events and underwent a detailed postmortem examination. Blood, saliva, urine, feces, and organs were collected for virus detection. Dog 1 had mild fever and lethargy while dog 2 experienced a possible seizure 5.5 hours after first virus administration. Viral DNA declined quickly in the blood after virus administration in both dogs but was still detectable 1 week later by quantitative polymerase chain reaction. Only samples taken directly after virus infusion contained infectious virus. Small amounts of viral DNA, but no infectious virus, were detected in a few saliva and urine samples. Necropsies did not reveal any relevant pathological changes and virus DNA was detected mainly in the spleen. The dogs in the study did not have cancer, and thus adverse events could be more common and viral load higher in dogs with tumors which allow viral amplification.
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
Karoliina
K
Autio
Finnish Centre for Laboratory Animal Pathology and Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki , Helsinki, Finland.
Anna
A
Knuuttila
Finnish Centre for Laboratory Animal Pathology and Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki , Helsinki, Finland.
Anja
A
Kipar
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki , Helsinki, Finland.
Sari
S
Pesonen
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki , Helsinki, Finland.
Kilian
K
Guse
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki , Helsinki, Finland.
Suvi
S
Parviainen
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki , Helsinki, Finland.
Minna
M
Rajamäki
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki , Helsinki, Finland.
Outi
O
Laitinen-Vapaavuori
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki , Helsinki, Finland.
Markus
M
Vähä-Koskela
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Anna
A
Kanerva
Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki , Helsinki, Finland.
Akseli
A
Hemminki