NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine

Cancer Immunol Res. 2017 Mar;5(3):211-221. doi: 10.1158/2326-6066.CIR-16-0162. Epub 2017 Feb 3.

Abstract

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 infected ex vivo with 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.

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Chemotaxis / immunology*
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Female
  • Genetic Vectors / genetics
  • Humans
  • Interleukin-12 / genetics*
  • Interleukin-12 / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / immunology
  • Melanoma, Experimental
  • Mice
  • Oncolytic Viruses / genetics
  • Peritoneal Neoplasms / genetics*
  • Peritoneal Neoplasms / immunology*
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / therapy
  • Transduction, Genetic

Substances

  • Cancer Vaccines
  • Cytokines
  • Interleukin-12

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