PULMONARY BIOLOGY OF ANTI-INTERLEUKIN-5 ANTIBODIES

Interleukin 5 (IL-5) is a critical cytokine for the maturation of eosi nophil precursors to eosinophils in the bone marrow and those eosinoph ils then accumulate in the lungs during asthma. We have studied anti I L-5 antibodies on allergic responses in mice, guinea pigs and monkeys and are extending this experiment into humans with a humanized antibod y. In a monkey model of pulmonary inflammation and air-way hyperreacti vity, we found that the TRFK-5 antibody blocked both responses for thr ee months following a single dose of 0.3 mg/kg, i.v. This antibody als o blocked lung eosinophilia in mice by inhibiting release from the bon e marrow. To facilitate multiple dosing and to reduce immunogenicity i n humans, we prepared Sch 55700, a humanized antibody against IL-5. Sc h 55700 was also active against lung eosinophilia in allergic monkeys and mice and against pulmonary eosinophilia and air-way hyperresponsiv eness in guinea pigs. Furthermore, as opposed to steroids, Sch 55700 d id not Cause immunosuppression in guinea pigs. Studies with this antib ody in humans will be critical to establishing the therapeutic potenti al of IL-5 inhibition.