Interleukin-2 liposomes for primary immune deficiency using the aerosol route

This is the first report of aerosol interleukin 2 (IL-2) liposome administration to individuals with immune deficiency. Parenteral IL-2 therapy has shown beneficial effects in some patients with cancer, common variable immunodeficiency (CVID), and human immunodeficiency vir-us (HIV) but is problematic because of side effects including fever and malaise as well as local swelling (delayed type hypersensitivity like reaction) after each subcutaneous IL-2 injection. Provision of an IL-2:human albumin liposome formulation via the aerosol route had few side effects in a recent clinical trial in cancer patients. Details of good manufacturing practice (GMP) synthesis and analysis of IL-2 liposomes (N = 6 lots) made without albumin carrier protein and placebo liposomes (three lots) are presented. After centrifugation, IL-2 was closely associated with the liposome pellet (99%). Mean diameter of liposomes was 1.1 mum. Patient acceptance, safety, toxicity, and immune effects of IL-2 liposomes were studied in individuals with primary immune deficiency (N = 15) and subsequently, a larger cohort of patients with hepatitis C. Experience in the immune deficient patients is the subject of this report. Placebo liposomes (12 weeks) and IL-2 liposomes (12 weeks) were provided using a nebulizer. Aerosol placebo liposomes and IL-2 liposomes were well tolerated. No changes in chest X-ray or pulmonary function were seen. Since biologic activity of aerosol IL-2 liposomes has been seen in viral disease (hepatitis Q, additional studies of aerosol IL-2 liposomes in individuals with hepatitis C and HIV are Planned. (C) 2002 Elsevier Science B.V. All rights reserved.