Antibody-cytokine fusion proteins for the therapy of cancer

Advances in genetic engineering and expression systems have led to rapid pr ogress in the development of antibodies fused to other proteins. These 'ant ibody fusion proteins' have novel properties and include antibodies with sp ecificity for tumor associated antigens fused to cytokines such as interleu kin-2 (IL2), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-12 (IL12). The goal of this approach to cancer therapy is to c oncentrate the cytokine in the tumor microenvironment and in so doing direc tly enhance the tumoricidal effect of the antibody and/or enhance the host immune response (T-cell, B-cell or NK) against the tumor. In the past decad e, multiple antibody-cytokine fusion proteins have been developed with diff erent specificities targeting a broad variety of tumors. These novel molecu les retain both antibody and cytokine associated functions. In addition, in animals bearing tumors, antibody-cytokine fusion proteins are able to targ et the tumor and to elicit a significant anti-tumor response that in some c ases results in a complete elimination of the tumor. These results suggest that antibody-cytokine fusion proteins have potential for use in the treatm ent of human cancer. In the present review, we describe strategies for cons truction of antibody-cytokine fusion proteins and discuss the properties of several antibody-cytokine fusion proteins with IgG genetically fused to th e cytokines IL2, GM-CSF or IL12. (C) 2001 Elsevier Science B.V. All rights reserved.