Antibody Therapy of Cancer

Monoclonal Antibody Therapy of Cancer A. General Considerations 

Of all of the potential applications of mAh therapy, cancer treatment has been the most intensively studied. A broad array of antigenic targets and antibody constructs have been evaluated since the advent of mAh technology in 1975, including two decades of clinical trials. Despite 

Heterogeneity of expression Shed antigen Immunogenicity Tumor penetration 

One of the earliest attempts to exploit hybridoma technology for cancer treatment was the work of Levy and co-workers, who produced mAbs reactive with the idiotype expressed on malignant B lymphocytes obtained from individual patients (157-158). Although the need to produce custom-made mAbs for each patient has severely limited the feasibility of this strategy, these pioneering studies did provide early and convincing evidence that mAb therapy could elicit durable antitumor responses. 

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Adams GP, Weiner LM. Monoclonal antibody therapy of cancer, Nature Biotechnology 23 1147-1157 (2005). 

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Weiner, L.M. An overview of monoclonal antibody therapy of cancer. Semin. Oncol. 1999, 26 (4 Suppl. 12), 41-50. 

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Saleh MN, LoBuglio AF, Trail PA, In Monoclonal Antibody-Based Therapy of Cancer (Ed. Grossband M), pp. 397 16. Marcel Dekker, New York, 1998. 

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Saleh, M. N., LoBuglio, A. F. and Trail, P. A. (1998) Monoclonal antibody-based immunocon-jugate therapy of cancer studies with BR96-doxorubicin. Basic and Clinical Oncology, 15, 397—416. 

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Goldenberg, D.M. Advancing role of radiolabeled antibodies in the therapy of cancer. Cancer Immunol. Immunother. 2003, 52, 281— 296. 

In this section we will discuss the most extensively studied tumor markers and the corresponding monoclonal antibodies that have been approved by the FDA (US Food and Drug Administration www.fda.gov) and in Europe for the imaging and therapy of cancer, or that are currently being developed. 

Armexin A1 emerged as a promising antigen for the radiolabeled antibody-based imaging and therapy of cancer [100]. In our laboratory, we use terminal perfusion protocols featuring active esters of biotin for the selective chemical labeling of accessible proteins in vascular structures. Biotinylated proteins are then purified from different organs (collected separately) and are submitted to a comparative proteomic analysis [106]. 

Knox SJ et al. Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clinical Cancer Research 1996 2 457-470. 

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