SUPPRESSION OF HUMAN PROSTATE CARCINOMA METASTASES IN SEVERE COMBINEDIMMUNODEFICIENT MICE BY INTERLEUKIN-2 IMMUNOCYTOKINE THERAPY

Immunocytokines are antibody-cytokine fusion proteins that combine the unique targeting ability of antibodies with the multifunctional activ ities of cytokines to activate effector cells in the tumor microenviro nment. Here, we demonstrate the therapeutic efficacy of a tumor-specif ic immunocytokine, huKS1/4-IL2, which effectively inhibited growth and dissemination of lung and bone marrow metastases of human prostate ca rcinoma in severe combined immunodeficient mice. This antitumor effect was specific and highly effective, irrespective of reconstitution of these mice with human lymphokine-activated killer cells. Survival time s of mice treated with huKS1/4-IL2 were increased 4-fold as compared w ith animals treated with a mixture of the corresponding antibody and r ecombinant human interleukin-2 (rhIL2). A persistent antitumor respons e after treatment with the huKS1/4-IL2 immunocytokine in B, T, and nat ural killer cell-deficient severe combined immunodeficient-BEIGE mice, depleted of granulocytes, implies a major role for macrophages in thi s treatment effect. Our data demonstrate that immunocytokine-directed interleukin-2 therapy to tumor sites is an immunotherapeutic approach with potent effects against disseminated metastases of human prostate carcinoma and suggest that this treatment could be effective in an adj uvant setting for patients with minimal residual disease.