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, we will chemically modify IL-2 so that it can be preferentially absorbed via lymphatics. We intend to modify IL-2 by rendering it more lipophilic, more resistant to acid hydrolysis and more 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. By virtue of the increased size of IL-2 (more than 40 kD), the molecule 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 activities of the modified IL-2 will be also be determined in vivo.Awardee's statement of the potential commercial applications of the research:Research suggests potential applications for lymphokines including interferons, interleukin tumor necrosis factor and lymphotoxin in the treatment of neoplastic, parasitic, viral, allergic and inflammatory diseases. In health care, an oral dosage form of equal therapeutic value is preferred to a parenteral form, because of greater patient acceptance and the lower cost of administration. A successful product may have better therapeutic characteristics than existing lymphokine medicines.National Cancer Institute (NCI)
