Abstract

The in vivo pharmacokinetics and efficacy of cationized human immunoglobulins in the human-peripheral blood lymphocytes-severe combined immune deficiency mouse model were evaluated in the present studies using the severe combined immunodeficient mouse transplanted with human lymphocytes and infected with human immunodeficiency virus (HIV)-1. Immunoglobulins from noninfected humans and from HIV-infected individuals were cationized. The pharmacokinetic analysis showed that the cationized immunoglobulins have a markedly reduced mean residence time and a marked increase in organ uptake compared to the native immunoglobulins. The toxicity studies performed with homologous immunoglobulins in BALB/c mice demonstrated cationized homologous immunoglobulins have no tissue toxicity at a daily dose of 7.5 mg/kg. Treatment of HIV-infected severe combined immune deficiency mice that were transplanted with human lymphocytes demonstrated therapeutic efficacy for a 2-week treatment at a dose of 5 mg/kg cationized HIV immune globulin. In conclusion, cationized immunoglobulins are potential antibody-based therapeutics for the treatment of acquired immune deficiency syndrome; cationized antibodies undergo enhanced transport into lymphocytes and when homologous cationized immunoglobulins are administered there is no measurable tissue toxicity.