Disseminated neuroectodermal tumors melanoma and neuroblastoma are refractory to most current therapeutic protocols and still have a very poor prognosis. Systemic delivery of cytotoxic drugs is often unsuccessful and dosage scaling is hampered by severe toxicity.

An emerging modality of antitumor treatment is represented by packaging high concentrations of cytotoxic drugs into stabilized liposomes which, per se, tend to extravasate preferentially and to accumulate into tumor interstitial fluids due to the defective structure of new vessels in tumor masses. A strong improvement of this inherent relative tumor selectivity of stabilized liposomes can be further provided by coupling tumor- specific antibodies to the outer surface of the lipidic envelop in a suitable orientation (immunoliposomes).

Disialoganglioside GD2 is abundantly expressed on both melanoma and neuroblastoma cells, while its expression in normal tissues is very restricted and quantitatively limited. Monoclonal antibodies recognizing GD2 bind to neuroblastoma and melanoma cells, with high affinity and specificity and represent an excellent tool for tumor targeting of immunoliposomes. In this article we have first explored the feasibility of anti-GD2 stabilized immunoliposomes. Anti-GD2 immunoliposomes have been loaded with different antitumor agents: i) fenretinide (HPR), a synthetic retinoid whose powerful apoptogenic properties have been demonstrated in neuroblastoma cells and appear presently to affect also melanoma cells, ii) iodine-labeled metaiodobenzylguanidine, a radiopharmaceutical endowed with a relative neural-tissue selectivity, presently used in its free form for the radioimaging and radiometabolic therapy of neuroectodermal tumors. Once synthesized, drug-loaded anti-GD2 immunoliposomes have been evaluated for their ability to selectively bind to and vehiculate their content into established melanoma and neuroblastoma cell lines in vitro. The biological effects of HPR-loaded immunoliposomes have then been assessed in terms of their ability to induce apoptosis or suppress the growth of the above tumor targets, as compared to the activity of comparable amounts of free drug.

Tumor targeting with anticancer agents-loaded immunoliposomes represents a novel, and potentially very rewarding approach to treatment of refractory neoplasias.