TY - JOUR
T1 - Anti-IL-10R antibody improves the therapeutic efficacy of targeted liposomal oligonucleotides
AU - Brignole, Chiara
AU - Marimpietri, Danilo
AU - Pastorino, Fabio
AU - Di Paolo, Daniela
AU - Pagnan, Gabriella
AU - Loi, Monica
AU - Piccardi, Federica
AU - Cilli, Michele
AU - Tradori-Cappai, Andrea
AU - Arrigoni, Gianluigi
AU - Pistoia, Vito
AU - Ponzoni, Mirco
PY - 2009/9/1
Y1 - 2009/9/1
N2 - 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.
AB - 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.
KW - Anti-IL-10R antibody
KW - Combination immunotherapy
KW - CpG oligodeoxynucleotides
KW - Neuroblastoma
KW - Targeted liposomes
UR - http://www.scopus.com/inward/record.url?scp=67651235587&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67651235587&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.05.006
DO - 10.1016/j.jconrel.2009.05.006
M3 - Article
C2 - 19427884
AN - SCOPUS:67651235587
VL - 138
SP - 122
EP - 127
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2
ER -