Abstract: The invention relates to the formation of multivalent antibody constructs for testing and therapeutic purposes. In one embodiment the constructs consist of antibodies or antibody fragments conjugated to liposomes. The constructs are employed in a cell-based in vitro assay for comparing the therapeutic activity of antibodies or antibody fragments in multivalent form to the same antibodies or fragments in bivalent, free form. The assay is useful for identifying antibodies having potential in vivo activity. Selected antibodies may then be tested in an animal model of a disease state, such as cancer or an autoimmune disorder. Co-delivery of antibodies and chemotherapeutics may also be investigated. In accordance with the invention, a significant enhancement in the activity of antibodies such as trastuzumab and rituximab was observed when these antibodies were presented in the multivalent liposomal form.

Abstract: The liposomes of the invention have a reactive surface that demonstrates reduced interaction with macromolecules and increased blood circulation time. The reactive surface may comprise phosphatidylserine. The liposomes are protected by the presence of high levels of a hydrophilic polymer conjugated to a lipid. The invention further provides means for adjusting the appropriate ratio of hydrophilic polymer to a reactive lipid by a) determining the reactivity of the lipid; b) determining the time required for the carrier to reach its desired target location; c) determining the affinity of desired interactions with the reactive surface; and d) incorporating in the liposome or lipid carrier the amount of polyethylene glycol required to protect the reactive surface.