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Monoclonal antibody therapy of cancer

Abstract

The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti–vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti–epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung. Cetuximab, used alone or with salvage chemotherapy, produces clinically meaningful anti-tumor responses in patients with chemotherapy-refractory cancers of the colon and rectum. In addition, the anti-HER2/neu antibody trastuzumab (Herceptin), in combination with standard adjuvant chemotherapy, has been shown to reduce relapses and prolong disease-free and overall survival in high-risk patients after definitive local therapy for breast cancer. These exciting recent results provide optimism for the development of mAbs that bind novel targets, exploit novel mechanisms of action or possess improved tumor targeting. Progress in the clinical use of radioimmunoconjugates remains hindered by complexity of administration, toxicity concerns and insufficiently selective tumor targeting.

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Figure 1: ADCC-mediated adaptive immunity switch.

Katie Ris

Figure 2: Complement-directed cytotoxicity.

Katie Ris

Figure 3: Examples of antibody-mediated signaling inhibition.

Katie Ris

Figure 4: Antibody-directed enzyme prodrug therapy (ADEPT).

Katie Ris

Figure 5: Potential targets for antibody therapy of cancer.

Katie Ris

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Correspondence to Louis M Weiner.

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G.P.A. is a consultant, scientific advisory board member and shareholder of EvoGenix and has received support for a research program from General Electric Global Research. L.M.W. is a consultant to Abgenix.

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Adams, G., Weiner, L. Monoclonal antibody therapy of cancer. Nat Biotechnol 23, 1147–1157 (2005). https://doi.org/10.1038/nbt1137

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