Oncolytic vaccinia virus as an adjuvant treatment to cytoreductive surgery for malignant peritoneal mesothelioma.
BACKGROUND
Malignant peritoneal mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. This experimental study aimed to examine the potential of modified vaccinia virus (VV) to treat MPM when administered alone or as an adjuvant treatment to surgery.


METHODS
Two aggressive murine mesothelioma cell lines (AC29, AB12), were used. Cell viability and viral cytopathic effects were assessed using MTS and crystal violet assays. Immunocompetent mice were injected intraperitoneally with MPM cells and treated with intraperitoneal VV. Tumor-bearing mice also underwent cytoreductive surgery (CRS) followed by VV (or control) therapy.


RESULTS
The cytotoxic effects of VV on MPM cell lines was significantly increased compared with the control non-cancer cell line. In both orthotopic models, VV induced tumor regression, prolonging median and long-term survival. VV treatment after incomplete CRS was not superior to VV alone; however, when mice with microscopic disease were treated with VV, further prolongation of median and long-term survivals was observed.


CONCLUSIONS
VV selectively kills MPM cells in vitro and leads to improved survival and cures in immunocompetent murine models. Higher efficacy of the virus in the microscopic disease context suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of VV in humans as a novel treatment for MPM.
Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Sergio A
SA
Acuna
Kathryn
K
Ottolino-Perry
Besmira
B
Çako
Nan
N
Tang
Fernando A
FA
Angarita
J Andrea
JA
McCart
D000276:Adjuvants, Immunologic; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D065426:Cytoreduction Surgical Procedures; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000086002:Mesothelioma, Malignant; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D050130:Oncolytic Virotherapy; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000502:physiology*; D014779:Virus Replication
D000276:Adjuvants, Immunologic