Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy.
Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Markus
M
Vähä-Koskela
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Siri
S
Tähtinen
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Susanna
S
Grönberg-Vähä-Koskela
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Kristian
K
Taipale
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Dipongkor
D
Saha
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Maiju
M
Merisalo-Soikkeli
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Marko
M
Ahonen
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki , Helsinki, Finland.
Noora
N
Rouvinen-Lagerström
Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Immunovirotherapy Group, University of Helsinki , Helsinki, Finland.
Mari
M
Hirvinen
Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health , Helsinki, Finland.
Ville
V
Veckman
Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health , Helsinki, Finland.
Sampsa
S
Matikainen
Advanced Microscopy Unit, Haartman Institute, University of Helsinki , Helsinki, Finland.
Fang
F
Zhao
Department of Obstetrics and Gynecology, Helsinki University Central Hospital , Helsinki, Finland.
Päivi
P
Pakarinen
Division of General Thoracic and Esophageal Surgery, Department of Cardiothoracic Surgery, Helsinki University Central Hospital , Helsinki, Finland.
Jarmo
J
Salo
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
Anna
A
Kanerva
Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Immunovirotherapy Group, University of Helsinki , Helsinki, Finland.
Vincenzo
V
Cerullo
Department of Pathology and Transplantation Laboratory, Cancer Gene Therapy Group, Haartman Institute, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, Finland.
Akseli
A
Hemminki