ENHANCEMENT OF TUMOR UPTAKE OF MONOCLONAL-ANTIBODY IN NUDE-MICE WITH PEG IL-2

Antibodies, both unconjugated and conjugated to toxins, have been reported to be effective treatment for some cancers and toxicity has been modest. However, the results have not been as dramatic as expected considering the unique specificity of targeting of monoclonal antibodies. This appears to be due in part to disappointingly low accumulation of antibody in the tumor relative to that administered. While interleukin 2 (IL-2) is not known to have significant, specific targeting for cancer, it's use has led to therapeutic results in a few cancers. Toxicity, primarily a vascular leakage syndrome, has severely restricted this treatment. Because the vessel walls represent a barrier to the egress of large molecules like immunoglobulins, we examined the potential of rIL-2 modified by conjugation with polyethylene glycol (PEG-IL-2) to increase tumor uptake of a monoclonal antibody, Lym-1, in nude mice implanted with Raji human lymphoma. A dose dependent enhancement of tumor concentration of antibody was observed after a single injection of PEG-IL-2. The maximum enhancement of tumor concentration of antibody by PEG-IL-2 was a factor of two-times. The interval of time between injection of PEG-IL-2 and injection of the antibody was also significant. No toxicity, but some increase in wet-weight and decrease in antibody concentration in most non-tumored tissues, was observed at doses of PEG-IL-2 of 8,000-80,000 IU. These results provide evidence for the potential of relatively nontoxic doses of PEG-IL-2 to enhance the efficacy of cancer treatment with monoclonal antibodies. In addition to the impetus for similar studies in patients, these observations justify additional studies to explore the mechanisms of action of IL-2 in the nude mouse.