Development of Fab′ fragments of anti-GD2 immunoliposomes entrapping doxorubicin for experimental therapy of human neuroblastoma

Chiara Brignole, Danilo Marimpietri, Claudio Gambini, Theresa M. Allen, Mirco Ponzoni, Fabio Pastorino

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. Since intensive therapeutic intervention does not prolong the overall disease-free survival rate for this tumor, novel therapeutic strategies are required. NB tumor, but not normal tissues, over-express the disialoganglioside (GD2) at the cell surface. In this study we developed a novel immunoliposomal formulation by covalently coupled Fab′ fragments of the monoclonal antibody anti-GD2 to Stealth liposomes (Fab′-SIL). In vitro experiments showed specific, competitive binding to, and uptake by various NB cell lines. Moreover, doxorubicin-loaded immunoliposomes (Fab′-SIL[DXR]) presented increased selectivity and efficacy in inhibiting NB cell proliferation compared to free drug and non-targeted liposomes (SL[DXR]). The in vivo cytotoxic effectiveness of different liposomal formulations encapsulating DXR was tested against an experimental metastatic model of human NB in nude mice. Long term survivors were obtained in mice treated with Fab′-SIL[DXR], but not in untreated animals or those treated with free anti-GD2 Fab′ fragments, Fab′-SIL (no drug), free-DXR or SL[DXR] (P

Original languageEnglish
Pages (from-to)199-204
Number of pages6
JournalCancer Letters
Volume197
Issue number1-2
DOIs
Publication statusPublished - Jul 18 2003

Fingerprint

Immunoglobulin Fab Fragments
Investigational Therapies
Neuroblastoma
Doxorubicin
Liposomes
Neoplasms
Competitive Binding
Nude Mice
Pharmaceutical Preparations
Disease-Free Survival
Survivors
Theoretical Models
Survival Rate
Monoclonal Antibodies
Cell Proliferation
Cell Line
Therapeutics

Keywords

  • Doxorubicin
  • Fab′ fragments of anti-GD
  • Immunoliposomes
  • Liposomes
  • Neuroblastoma
  • Nude mice
  • Targeted drug delivery
  • Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

@article{20bb592a106d434da28f3bf0dddcbb8a,
title = "Development of Fab′ fragments of anti-GD2 immunoliposomes entrapping doxorubicin for experimental therapy of human neuroblastoma",
abstract = "Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. Since intensive therapeutic intervention does not prolong the overall disease-free survival rate for this tumor, novel therapeutic strategies are required. NB tumor, but not normal tissues, over-express the disialoganglioside (GD2) at the cell surface. In this study we developed a novel immunoliposomal formulation by covalently coupled Fab′ fragments of the monoclonal antibody anti-GD2 to Stealth liposomes (Fab′-SIL). In vitro experiments showed specific, competitive binding to, and uptake by various NB cell lines. Moreover, doxorubicin-loaded immunoliposomes (Fab′-SIL[DXR]) presented increased selectivity and efficacy in inhibiting NB cell proliferation compared to free drug and non-targeted liposomes (SL[DXR]). The in vivo cytotoxic effectiveness of different liposomal formulations encapsulating DXR was tested against an experimental metastatic model of human NB in nude mice. Long term survivors were obtained in mice treated with Fab′-SIL[DXR], but not in untreated animals or those treated with free anti-GD2 Fab′ fragments, Fab′-SIL (no drug), free-DXR or SL[DXR] (P",
keywords = "Doxorubicin, Fab′ fragments of anti-GD, Immunoliposomes, Liposomes, Neuroblastoma, Nude mice, Targeted drug delivery, Therapy",
author = "Chiara Brignole and Danilo Marimpietri and Claudio Gambini and Allen, {Theresa M.} and Mirco Ponzoni and Fabio Pastorino",
year = "2003",
month = "7",
day = "18",
doi = "10.1016/S0304-3835(03)00099-5",
language = "English",
volume = "197",
pages = "199--204",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Development of Fab′ fragments of anti-GD2 immunoliposomes entrapping doxorubicin for experimental therapy of human neuroblastoma

AU - Brignole, Chiara

AU - Marimpietri, Danilo

AU - Gambini, Claudio

AU - Allen, Theresa M.

AU - Ponzoni, Mirco

AU - Pastorino, Fabio

PY - 2003/7/18

Y1 - 2003/7/18

N2 - Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. Since intensive therapeutic intervention does not prolong the overall disease-free survival rate for this tumor, novel therapeutic strategies are required. NB tumor, but not normal tissues, over-express the disialoganglioside (GD2) at the cell surface. In this study we developed a novel immunoliposomal formulation by covalently coupled Fab′ fragments of the monoclonal antibody anti-GD2 to Stealth liposomes (Fab′-SIL). In vitro experiments showed specific, competitive binding to, and uptake by various NB cell lines. Moreover, doxorubicin-loaded immunoliposomes (Fab′-SIL[DXR]) presented increased selectivity and efficacy in inhibiting NB cell proliferation compared to free drug and non-targeted liposomes (SL[DXR]). The in vivo cytotoxic effectiveness of different liposomal formulations encapsulating DXR was tested against an experimental metastatic model of human NB in nude mice. Long term survivors were obtained in mice treated with Fab′-SIL[DXR], but not in untreated animals or those treated with free anti-GD2 Fab′ fragments, Fab′-SIL (no drug), free-DXR or SL[DXR] (P

AB - Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. Since intensive therapeutic intervention does not prolong the overall disease-free survival rate for this tumor, novel therapeutic strategies are required. NB tumor, but not normal tissues, over-express the disialoganglioside (GD2) at the cell surface. In this study we developed a novel immunoliposomal formulation by covalently coupled Fab′ fragments of the monoclonal antibody anti-GD2 to Stealth liposomes (Fab′-SIL). In vitro experiments showed specific, competitive binding to, and uptake by various NB cell lines. Moreover, doxorubicin-loaded immunoliposomes (Fab′-SIL[DXR]) presented increased selectivity and efficacy in inhibiting NB cell proliferation compared to free drug and non-targeted liposomes (SL[DXR]). The in vivo cytotoxic effectiveness of different liposomal formulations encapsulating DXR was tested against an experimental metastatic model of human NB in nude mice. Long term survivors were obtained in mice treated with Fab′-SIL[DXR], but not in untreated animals or those treated with free anti-GD2 Fab′ fragments, Fab′-SIL (no drug), free-DXR or SL[DXR] (P

KW - Doxorubicin

KW - Fab′ fragments of anti-GD

KW - Immunoliposomes

KW - Liposomes

KW - Neuroblastoma

KW - Nude mice

KW - Targeted drug delivery

KW - Therapy

UR - http://www.scopus.com/inward/record.url?scp=0038105280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038105280&partnerID=8YFLogxK

U2 - 10.1016/S0304-3835(03)00099-5

DO - 10.1016/S0304-3835(03)00099-5

M3 - Article

VL - 197

SP - 199

EP - 204

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 1-2

ER -