Immunoliposomes that optimize internalization into target cells

DETAILED DESCRIPTION The present invention provides novel immunoliposomes optimized for delivering therapeutic agents to the cytoplasm of a target cell.
These immunoliposomes exhibit increased half-life in blood, are capable of specifically targeting particular cells, and are capable of being internalized into the cytoplasm by the target cells thereby avoiding loss of the therapeutic agents or degradation by the endolysosomal pathway.
Thus, in one preferred embodiment this invention provides for immunoliposomes that optimize internalization of a therapeutic agent into the cytoplasm of a cell bearing a characteristic cell surface marker.
These immunoliposomes comprise an Fab' domain of an antibody wherein the Fab' domain specifically binds the characteristic marker, an amphipathic vesicle-forming lipid that forms a liposome, a polyethylene glycol derivatized lipid wherein the polyethylene glycol has an average molecular weight of between about 750 D and 5000 D, more preferably between about 1200 D and about 3000 D, most preferably about 1900 D, and a therapeutic agent contained within the liposome.
The derivatized lipid is present at up to about 1.
2 mole percent, more preferably at up to about 2.
4 mole percent, and most preferably at up to about 3.
6 mole percent of total lipid.
Preferred characteristic markers include growth factor receptors.
Particularly preferred are growth factor receptors including HER1, HER2, HER3 and HER4 with HER2 being most preferred.
The Fab' domain may be a humanized Fab' domain, more specifically a humanized Fab' domain of an anti-HER2 monoclonal antibody.
The growth-inhibiting immunoliposome may further comprise a maleimide-derivatized phosphatidylethanolamine (M-PE) which forms a thioether linkage to the Fab' domain of an antibody.
The vesicle forming lipid may include a phospholipid, a glycolipid, a sphingolipid, or a sterol.
The immunoliposomes have an average diameter that ranges from about 50 nm to about 500 nm, more preferably about 75 nm to about 300 nm and most preferably is about 100 nm