Therapeutic Antibodies Against Cancer

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mAbs approved for clinical use

At present 13 mAbs are approved for clinical use in the European Union or the United States (see Table 1). One of the approved mAbs, gemtuzumab ozogamicin (Mylotarg), was withdrawn from the market because of lack of clinical benefit and safety reasons after a clinical trial in which a greater number of deaths occurred in the group of patients with acute myeloid leukemia (AML) who received Mylotarg compared with those receiving chemotherapy alone. Mylotarg, catumaxumab (Removab) (not yet

mAbs in clinical and preclinical development

Hundreds of mAbs are in thousands of clinical trials14; 2239 entries for planned, ongoing, or completed clinical trials were retrieved from http://www.clinicaltrials.gov by searching with cancer AND therapy AND monoclonal antibodies as of August 2011, of which 270 are in phase III. A significant number of all new medicines are mAbs against cancer (see also http://www.phrma.org/research/new-medicines). At least 1 to 3 different antibodies are being developed at different companies for each

Safety, efficacy, and quality of candidate therapeutic mAbs

The success of antibody-based therapeutics is mostly attributable to the use of concepts and methodologies developed during a paradigm change decades ago that resulted in dramatic improvement of 3 key features in candidate therapeutics required for FDA approval: safety, efficacy, and quality. These factors are critical for the success of any drug, and are discussed in more detail as regards antibody-based therapeutics.

Biosimilar and biobetter therapeutic antibodies

A major goal of current activity is to develop therapeutic antibodies that are similar but cheaper than the currently existing ones, or are better in terms of efficacy and safety. By 2015 biologics worth $60 billion in annual sales will lose patent protection, bolstering hopes for the rapid growth of the biosimilars as generics companies elbow their way into a large new market. Rituxan/MabThera and Remicade are on the top of the list for biosimilars. Sandoz, for example, which is leading the

Summary

The rapid progress made in the last few decades toward the development of potent therapeutic antibodies raises several questions for the future directions of this field. A key question is whether there are any indications of a paradigm change that could lead to radically different therapeutics, as occurred 2 to 3 decades ago, and which resulted in an explosion of antibody therapeutics approved for clinical use during the last decades. If history provides an answer and such a paradigm shift

Acknowledgments

The authors would like to thank John Owens from the group Protein Interactions for discussions and help.

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    This study was supported by the NIH NCI CCR intramural program.

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