Interaction of differently designed immunoliposomes with colon cancer cells and Kupffer cells. An in vitro comparison.
OBJECTIVE
Evaluate the effectiveness of distal-end coupling of a tumor-specific antibody to liposomal polyethylene glycol (PEG) chains to improve target binding and reduce interference by macrophage uptake.


METHODS
Monoclonal antibody CC52, specific for CC531 rat colon carcinoma, was coupled to the bilayer of PEG-liposomes (type I) or to the distal end of bilayer-anchored PEG-chains (type II). Uptake of both (radiolabeled)liposome types by CC531 cells and rat liver macrophages was determined.


RESULTS
With increasing antibody density, both immunoliposome types showed increased binding to target cells, but type II liposomes displayed better target recognition than type I. Uptake by macrophages increased with antibody density for both liposome types. Lowest uptake by macrophages was found for type II liposomes at low antibody densities. Unexpectedly, not only for type I but also for type II liposomes, in which the antibody is coupled via its Fc moiety, uptake by macrophages was inhibited by aggregated IgG, indicating involvement of Fc receptors. Also polyinosinic acid, an inhibitor of scavenger receptors, reduced uptake of type II liposomes.


CONCLUSIONS
Although distal end coupling of antibodies to bilayer-anchored PEG chains in liposomes through the Fc moiety enhances target cell binding, it does not prevent the recognition by Fc receptors on macrophages.
Koning
Gerben A
GA
Department of Cell Biology, Section Liposome Research, Groningen University Institute for Drug Exploration, Faculty of Medical Sciences, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Morselt
Henriëtte W M
HW
Gorter
Arko
A
Allen
Theresa M
TM
Zalipsky
Samuel
S
Scherphof
Gerrit L
GL
Kamps
Jan A A M
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D007728:Kupffer Cells; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D051116:Receptors, Scavenger
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D008081:Liposomes; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011092:Polyethylene Glycols