Anti-IL-10R antibody improves the therapeutic efficacy of targeted liposomal oligonucleotides

Chiara Brignole, Danilo Marimpietri, Fabio Pastorino, Daniela Di Paolo, Gabriella Pagnan, Monica Loi, Federica Piccardi, Michele Cilli, Andrea Tradori-Cappai, Gianluigi Arrigoni, Vito Pistoia, Mirco Ponzoni

Research output: Contribution to journalArticle

Abstract

High-risk Neuroblastoma (NB) has still a poor prognosis. Liposomes targeted to NB cells and encapsulating antisense CpG-containing oligonucleotides (TL-asCpG) had increased anti-tumour efficacy in NB xenografts compared to free asCpG. Interleukin 10 (IL-10) suppresses antigen presenting cell activation contributing to tumour-mediated immune suppression. In principle, combination of TL-asCpG and antibodies against IL-10 receptor (aIL-10R) could prolong immune system activation, leading to better therapeutic results. Mice treated with TL-asCpG 4 h after human NB cell inoculation survived significantly longer than controls. An increased life span was achieved also in mice receiving TL-asCpG 24 and 72 h after NB cell challenge. The addition of aIL-10R to TL-asCpG in the 4-h protocol significantly increased the percentage of long term survivors compared to TL-asCpG only. Surviving mice treated with the combined strategy were completely cured. In contrast, long term surviving mice treated only with TL-asCpG presented lymph node infiltration with NB cells. TL-asCpG plus aIL-10R treatment was significantly superior to TL-asCpG alone also for the 24-h protocol. Ex vivo experiments demonstrated that the combined therapy evoked a stronger and more prolonged immune system activation compared to monotherapy. These results support the feasibility of a clinical trial with TL-asCpG and aIL-10R in advanced NB patients.

Original languageEnglish
Pages (from-to)122-127
Number of pages6
JournalJournal of Controlled Release
Volume138
Issue number2
DOIs
Publication statusPublished - Sep 1 2009

Keywords

  • Anti-IL-10R antibody
  • Combination immunotherapy
  • CpG oligodeoxynucleotides
  • Neuroblastoma
  • Targeted liposomes

ASJC Scopus subject areas

  • Pharmaceutical Science

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