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

Cancer patients who are administered therapeutic doses of cytokines (e.g., interleukin-2, granulocyte macrophage colony stimulating factor, interleukin-12, and tumor necrosis factor-alpha) 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.