Clinical Development of Antibody-Fusion Proteins for Cancer Therapy

Abstract

Antibody-fusion proteins are new, promising derivatives of monoclonal antibodies mAbs), and some are being used for cancer therapy. Ongoing research efforts are increasing the repertoire and effi cacy of mAbs and mAb-based molecules for the treatment of cancer. Antibody-fusion proteins use the antigen recognition capabilities of the mAb to target a tumor antigen, bringing the fusion protein into the tumor microenvironment. Depending upon what other molecule is fused to the mAb component of the molecule such as other mAbs, cytokines, chemokines, and toxins), a variety of molecular and cellular activities can thereby be localized to the sites of tumor cells. In this review, we discuss different types of antibody-fusion proteins either in clinical trials or in development for multiple malignancies. We also discuss patient-intrinsic factors that affect therapeutic effi cacy, including the inhibitory KIR repertoire of a patient's NK cells and the affi nity of a patient's Fc receptors for the Fc portion of the mAb molecule. The level of sophistication of antibody-fusion proteins continues to increase with our understanding of patientintrinsic factors that affect individualized responses to therapy. New and promising fusion proteins that overcome patient-intrinsic limitations are an exciting application of this technology.