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Improved Therapeutic Efficacy of Doxorubicin-Loaded Long-Circulating Liposomes Targeted with Anti-Nuclesome Monoclonal Antibody 2C5 Against Various Tumors

T.A. ElBayoumi and V.P. Torchilin
Northeastern University, US

Keywords:
stealth liposomes, antinuclear autoantibody, tumor-targeting

Abstract:
The anticancer efficacy of Doxil®- commercial Stealth Doxorubicin liposomes – was markedly enhanced via the attachement of the antinuclear monoclonal antibody (mAb) 2C5, which specifically recognizes a broad variety of tumors via the tumor cell surface-bound nucleosomes, released by apoptotically dying neighboring tumor cells. The mAb 2C5-modified liposomes demonstrated 3-to-8- fold increase in cellular binding and uptake using diverse cancer lines, which lead to clear significant improvement in cytotoxicity against cancer cells in vitro, compared to control (non-specific or plain) formulations. Moreover, 111-In-radiolabeled liposomes targeted by the mAb 2C5 showed approx. 2-fold higher tumor-specific accumulation, with evident faster in vivo tumor visualization using gamma-scintigraphy, when compared to controls. Using different tumors in mice, the 2C5-Doxil® treatment achieved markedly significant decrease in primary tumor volumes and weights and reduced metastatic growths, in comparison to original or non-specific IgG-modified Doxil® treatments. Our results confirm the strong potential of the mAb 2C5-Doxil® as a tumor-targeted therapeutic formulation.

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