LYMPHATIC DELIVERY OF INTERLEUKIN-2

IL-2 IS CURRENTLY BEING EXAMINED AS AN ANTI-CANCER REAGENT IN CLINICAL TRAILS. IN THE MAJORITY OF THESE TRIALS, IL-2 HAS BEEN ADMINISTERED BY THE I.V. OR I.P. ROUTES WITH SOME DEGREE OF SUCCESS. SOME INVESTIGATORS HAVE SUGGESTED THAT LOW-DOSAGES OF IL-2 ADMINISTERED VIA LOCAL LYMPHATICS MAY BE AN EFFECTIVE APPROACH TO TUMOR THERAPY. THEREFORE, WE WILL CHEMICALLY MODIFY IL-2 SO THAT IT CAN BE PREFERENTIALLY ABSORBED VIA LYMPHATICS. SHE INTENDS TO MODIFY IL-2 BY RENDERING IT MORE A ) LIPOPHILIC B) RESISTANT TO ACID HYDROLYSIS AND C) ABLE TO CIRCUMVENT PORTAL VEIN ABSORPTION. TWO SANDWICH COMPLEXES ARE DESCRIBED IN DETAIL, ONE THAT WILL ALLOW IL-2 TO BE TRANSPORTED WITHIN CHYLOMICRONS AND THE OTHER WITHIN THE VLDL COMPARTMENT OF PLASMA. SHE ALSO SUGGESTS THAT BY VIRTUE OF THE INCREASED SIZE OF IL-2 (MORE THAN 40KD) THE MOELCULE WILL BE MORE LYMPHOTROPIC. WE WILL DETERMINE THE SIZE, BIOREACTIVITIES, ACID-RESISTANCE, AND HYDROLYTIC RESISTANCE OF THE TWO SANDWICH COMPLEXES OF IL-2 IN VITRO. THE PHARMACOKINETICS, BIOAVAILABILITIES AND ANTI-TUMOR ACITIVITIES OF THE MODIFIED IL-2 WILL ALSO BE DETERMINED IN VIVO.