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

作者：Brignole Chiara^*; Marimpietri Danilo; Pastorino Fabio; Di Paolo Daniela; Pagnan Gabriella; Loi Monica; Piccardi Federica; Cilli Michele; Tradori Cappai Andrea; Arrigoni Gianluigi; Pistoia Vito; Ponzoni Mirco

来源：Journal of Controlled Release, 2009, 138(2): 122-127.

DOI：10.1016/j.jconrel.2009.05.006

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

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.

• 出版日期2009-9-1