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 specificity of the Ab to target Fc functions or associated molecules to the site 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 IgG3-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 anti-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 activity 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 survivors showed some evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they are 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.