AN IGG3-IL-2 FUSION PROTEIN RECOGNIZING A MURINE B-CELL LYMPHOMA EXHIBITS EFFECTIVE TUMOR IMAGING AND ANTITUMOR-ACTIVITY

Antibody (Ab)-based tumor therapeutics use the tumor-binding specifici ty of the Ab to target Fc functions or associated molecules to the sit e of the tumor. We have used an Ab-interleukin-2 (IL-2) fusion protein to deliver IL-2 to a murine B cell lymphoma (38C13). This anti-Id IgG 3-C(H)3-IL-2, which recognizes the idiotype present on the surface of the lymphoma has a half-life in mice approximately 17-fold longer than the half-life reported for IL-2, Gamma camera studies showed that ant i-Id IgG3-C(H)3-IL-2 localizes at the site of a subcutaneous tumor in mice. The anti-Id IgG3-C(H)3-IL-2 also shows enhanced antitumor activi ty compared with the combination of Ab and IL-2 administered together. However, the mechanism of antitumor activity appears to depend on the dose and the treatment schedule used. A single dose of fusion protein prevented tumor in only 50% of the animals, although all the survivor s showed same evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they ar e ineffective in generating protective immunologic memory, Our results suggest that Ab-IL-2 fusion proteins will be useful in the diagnosis and treatment of human B cell lymphomas and other related malignancies .