Antibody-cytokine fusion proteins for the therapy of cancer.

Advances in genetic engineering and expression systems have led to rapid progress in the development of antibodies fused to other proteins. These 'antibody fusion proteins' have novel properties and include antibodies with specificity for tumor associated antigens fused to cytokines such as interleukin-2 (IL2), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-12 (IL12). The goal of this approach to cancer therapy is to concentrate the cytokine in the tumor microenvironment and in so doing directly 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 decade, multiple antibody-cytokine fusion proteins have been developed with different specificities targeting a broad variety of tumors. These novel molecules retain both antibody and cytokine associated functions. In addition, in animals bearing tumors, antibody-cytokine fusion proteins are able to target the tumor and to elicit a significant anti-tumor response that in some cases results in a complete elimination of the tumor. These results suggest that antibody-cytokine fusion proteins have potential for use in the treatment of human cancer. In the present review, we describe strategies for construction of antibody-cytokine fusion proteins and discuss the properties of several antibody-cytokine fusion proteins with IgG genetically fused to the cytokines IL2, GM-CSF or IL12.