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TheScientificWorldJOURNAL
Volume 10 (2010), Pages 2070-2089
http://dx.doi.org/10.1100/tsw.2010.191
Review Article

New Antibody Conjugates in Cancer Therapy

1Immunomedics, Inc., Morris Plains, NJ, USA
2Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, NJ, USA

Received 23 June 2010; Revised 14 September 2010; Accepted 20 September 2010

Academic Editor: Marc Lippman

Copyright © 2010 Serengulam V. Govindan and David M. Goldenberg.

Abstract

Targeting of radiation, drugs, and protein toxins to cancers selectively with monoclonal antibodies (MAbs) has been a topic of considerable interest and an area of continued development. Radioimmunotherapy (RAIT) of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled anti-CD22 MAb, 90Y-epratuzumab. The advantage of pretargeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models of lymphoma and solid tumors. Importantly, the advantages of combining RAIT with radiation sensitizers, with immunotherapy, or a drug conjugate targeting a different antigen are being studied clinically and preclinically. The area of drug-conjugated antibodies is progressing with encouraging data published for the trastuzumab-DM1 conjugate in a phase I clinical trial in HER2-positive breast cancer. The Dock-and-Lock platform technology has contributed to the design and the evaluation of complex antibody-cytokine and antibody-toxin conjugates. This review describes the advances made in these areas, with illustrations taken from advances made in the authors' institutions.