Antibody-cytokine fusion proteins: innovative weapons in the war against cancer

J. S. Dela Cruz1, T. H. Huang1, M. L. Penichet1 and S. L. Morrison1, 2

(1) Department of Microbiology, Immunology and Molecular Genetics, The Molecular Biology Institute, University of California at Los Angeles, Los Angleles, California, USA
(2) Department of Microbiology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA

Received: 18 November 2003 Accepted: 1 December 2003

Abstract. Cancer patients who are administered therapeutic doses of cytokines (e. g., interleukin-2, granulocyte macrophage colony stimulating factor, interleukin-12, and tumor necrosis factor-) frequently develop devastating toxic side effects that can lead to discontinuation of therapy. This problem has compelled numerous investigators to design innovative strategies that will reduce prolonged systemic cytokine exposure and promote cytokine accumulation at the site of the tumor. One such strategy involves the use of antibody-cytokine fusion proteins consisting of immunoenhancing cytokines genetically fused to antibodies that are able to target specific antigens exclusively expressed or overexpressed on the surface of tumor cells. Preclinical studies examining their therapeutic efficacy demonstrate that they posses potent tumoricidal activity, suggesting that they may be clinically useful as novel cancer therapeutic agents.
Key words Antibody fusion protein - Antibody - Cytokine - Cancer - Immunotherapy