Ultrasound-guided intra-tumor injection of combined immunotherapy cures mice from orthotopic prostate cancer

Giorgio Mauri, Claudia Chiodoni, Mariella Parenza, Ivano Arioli, Claudio Tripodo, Mario Paolo Colombo

Research output: Contribution to journalArticle

Abstract

Intra-tumor injection of immunotherapeutic agents is often the most effective, likely because of concomitant modification of tumor microenvironment. We tested an immunotherapeutic regimen consisting of CpG oligonucleotides and of adenovirus-mediated gene delivery of CCL16 chemokine directly into orthotopically implanted prostate tumors by ultrasound-guided injection, followed by systemic administration of an anti-IL-10R antibody. This combination treatment induced rapid stromal rearrangement, characterized by massive leukocyte infiltration and large areas of necrosis, a scenario that eventually led to complete tumor rejection and systemic immunity in 75 % of the treated mice. In vivo T lymphocyte depletion experiments demonstrated that the efficacy of CCL16/CpG/anti-IL-10R combination treatment relies upon CD8 T lymphocytes whereas CD4 T cells are dispensable. The results underlie the feasibility of echo-guided local immunotherapy of tumors located in visceral organs that are not easily accessible.

Original languageEnglish
Pages (from-to)1811-1819
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume62
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • CCL-16
  • Combination treatment
  • CpG oligonucleotides
  • Local cancer immunotherapy
  • Prostate tumor
  • Ultrasound-guided immunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

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