NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine.
Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infectedex vivowith an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year.Cancer Immunol Res; 5(3); 211-21. ©2017 AACR.
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.|Department of Laboratory Medicine, University of Tabuk, Tabuk, Saudi Arabia.|Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
Almohanad A
AA
Alkayyal
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
Lee-Hwa
LH
Tai
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
Michael A
MA
Kennedy
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
Christiano Tanese
CT
de Souza
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
Jiqing
J
Zhang
Apoptosis Research Centre, CHEO Research Institute, Ottawa, Ontario, Canada.
Charles
C
Lefebvre
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
Shalini
S
Sahi
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.|Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
Abhirami A
AA
Ananth
Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.|Department of Medical Technology, Taibah University, Medina, Saudi Arabia.
Ahmad Bakur
AB
Mahmoud
Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
Andrew P
AP
Makrigiannis
Department of Medical Imaging, University of Ottawa, Ottawa, Ontario, Canada.|Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada.
Greg O
GO
Cron
Department of Medical Imaging, University of Ottawa, Ottawa, Ontario, Canada.
Blair
B
Macdonald
Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada.
E Celia
EC
Marginean
Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.|Apoptosis Research Centre, CHEO Research Institute, Ottawa, Ontario, Canada.
David F
DF
Stojdl
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.|Department of BMI, University of Ottawa, Ottawa, Ontario, Canada.
John C
JC
Bell
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute. rauer@toh.ca.|Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.
Rebecca C
RC
Auer
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008546:Melanoma, Experimental; D051379:Mice; D050504:Oncolytic Viruses / Q000235:genetics; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D014161:Transduction, Genetic
D019496:Cancer Vaccines; D016207:Cytokines; D018664:Interleukin-12