TY - JOUR
T1 - Immunoliposomal fenretinide
T2 - A novel antitumoral drug for human neuroblastoma
AU - Raffaghello, L.
AU - Pagnan, G.
AU - Pastorino, F.
AU - Cosimo, E.
AU - Brignole, C.
AU - Marimpietri, D.
AU - Bogenmann, E.
AU - Ponzoni, M.
AU - Montaldo, P. G.
PY - 2003/7/18
Y1 - 2003/7/18
N2 - Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In advanced disease stages, prognosis is poor and treatments have limited efficacy, thus novel strategies are warranted. The synthetic retinoid fenretinide (HPR) induces apoptosis in NB and melanoma cell lines. We reported an in vitro potentiation of HPR effects on melanoma cells when the drug is incorporated into GD2-targeted immunoliposomes (anti-GD2-SIL-HPR). Here, we investigated the antitumor activity of anti-GD2-SIL-HPR against NB cells, both in vitro and in vivo. Anti-GD2-immunoliposomes (anti-GD2-SIL) showed specific, competitive binding to, and uptake by, various NB cell lines. Moreover, anti-GD2-SIL-HPR presented increased selectivity and efficacy in inhibiting NB cell proliferation through the induction of apoptosis, compared to free drug and SL-HPR. In an in vivo NB metastatic model, we demonstrated that anti-GD2-SIL-HPR completely inhibited the development of macroscopic and microscopic metastases in comparison to controls. However, similar, but significantly less potent antitumor effect was observed also in mice treated with anti-GD2 immunoliposomes without HPR (anti-GD2-SIL-blank) or anti-GD2 mAb alone (P=0.0297 and P=0.0294, respectively, vs. anti-GD2-SIL-HPR). Moreover, our results clearly demonstrated that, although anti-GD2 mAb had a strong antitumor effect in this in vivo NB model, 100% curability was obtained only following treatment with anti-GD2-SIL-HPR (P
AB - Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In advanced disease stages, prognosis is poor and treatments have limited efficacy, thus novel strategies are warranted. The synthetic retinoid fenretinide (HPR) induces apoptosis in NB and melanoma cell lines. We reported an in vitro potentiation of HPR effects on melanoma cells when the drug is incorporated into GD2-targeted immunoliposomes (anti-GD2-SIL-HPR). Here, we investigated the antitumor activity of anti-GD2-SIL-HPR against NB cells, both in vitro and in vivo. Anti-GD2-immunoliposomes (anti-GD2-SIL) showed specific, competitive binding to, and uptake by, various NB cell lines. Moreover, anti-GD2-SIL-HPR presented increased selectivity and efficacy in inhibiting NB cell proliferation through the induction of apoptosis, compared to free drug and SL-HPR. In an in vivo NB metastatic model, we demonstrated that anti-GD2-SIL-HPR completely inhibited the development of macroscopic and microscopic metastases in comparison to controls. However, similar, but significantly less potent antitumor effect was observed also in mice treated with anti-GD2 immunoliposomes without HPR (anti-GD2-SIL-blank) or anti-GD2 mAb alone (P=0.0297 and P=0.0294, respectively, vs. anti-GD2-SIL-HPR). Moreover, our results clearly demonstrated that, although anti-GD2 mAb had a strong antitumor effect in this in vivo NB model, 100% curability was obtained only following treatment with anti-GD2-SIL-HPR (P
KW - Adjuvant therapy
KW - Anti-GD2
KW - Apoptosis
KW - Fenretinide
KW - Immunolipsomes
KW - Liposomes
KW - Metastasis
KW - Neuroblastoma
KW - Retinoid
UR - http://www.scopus.com/inward/record.url?scp=0037767745&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037767745&partnerID=8YFLogxK
U2 - 10.1016/S0304-3835(03)00097-1
DO - 10.1016/S0304-3835(03)00097-1
M3 - Article
C2 - 12880975
AN - SCOPUS:0037767745
VL - 197
SP - 151
EP - 155
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1-2
ER -