Biopharmaceutics of liposomal interleukin 2, oncolipin.
Oncolipin is a multilamellar liposomal (dimyristoyl phosphatidylcholine) formulation of interleukin 2 (IL-2) and human serum albumin (HSA) with distinct surface characteristics which may influence its biological activities. IL-2 and HSA were detected on the surface of the liposomes using specific antibody staining. Surface expression of IL-2 was also demonstrated by the observation that Oncolipin bound to cells expressing IL-2 receptors (IL-2R) containing alphabetagamma or betagamma subunits. Binding and internalization of Oncolipin by cells expressing alphabetagamma or betagamma receptor subunits was blocked by excess free IL-2 or a neutralizing antibody against the beta chain. The display of surface IL-2 on Oncolipin's liposomes was maintained in vivo after intravenous injection into mice. IL-2 was also present between the lipid bilayers of the multilamellar liposomes based on the unique physical characteristics detected by freeze fracture electron microscopy. The bulk of the liposome-associated IL-2 was released from the liposomes upon incubation at 37 degrees C in medium containing serum, indicating that the IL-2 was not irreversibly entrapped on or in the liposome structure. Thus, Oncolipin is receptor-targeted to activated T and NK cells by virtue of its surface expression of IL-2 and has the potential to release IL-2 following deposition within lymphoid organs. These properties may confer distinct advantages over soluble IL-2 for immunotherapy of cancer and viral diseases.
Neville
M E
ME
Biomirma USA, Inc., 1002 Eastpark Blvd, Cranbury, NJ 08831, USA.
Boni
L T
LT
Pflug
L E
LE
Popescu
M C
MC
Robb
R J
RJ
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D005614:Freeze Fracturing; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D007694:Killer Cells, Natural / Q000378:metabolism; D008027:Light; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D011485:Protein Binding; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism; D012542:Scattering, Radiation; D012709:Serum Albumin / Q000096:biosynthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D000075462:Serum Albumin, Human; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D007376:Interleukin-2; D008051:Lipid Bilayers; D008081:Liposomes; D015375:Receptors, Interleukin-2; D012709:Serum Albumin; C420502:oncolipin; D000075462:Serum Albumin, Human