IL-2 is currently being examined as an anti-cancer reagent in clinical trials. 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, the applicant proposes to 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 40 kD) the molecule will be more lymphotropic. The applicant proposes to 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 activities of the modified IL-2 will be also be determined in vivo.
