From Laboratory to Clinic
In 1890 it was shown that resistance to diphtheria toxin could be transferred from one animal to another by transfer of serum (1 ). From this discovery, passive antibody therapy was developed as an effective treatment for infectious diseases and for neutr
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16 From Laboratory to Clinic The Story of CAMPATH-1 Geoff Hale and Herman Waldmann 1. Introduction In 1890 it was shown that resistance to diphtheria toxin could be transferred from one animal to another by transfer of serum (1). From this discovery, passive antibody therapy was developed as an effective treatment for infectious diseases and for neutralization of toxins, and continues to be used to this day. Meanwhile, there have been continued efforts to use antibodies for cancer therapy, starting with the pioneering work of Hericourt and Richet in 1895 (2), which was the forerunner of the “magic bullet” concept. However, all of the early work on tumor therapy led ultimately to disappointment (3). The problems were readily acknowledged, i.e., lack of specificity and reproducibility, lack of purity, and the xenogeneic immune response. Developments over the past 20 years, as described throughout this book, have effectively overcome all of these technical problems, often in very ingenious ways. The difficulty we have now is different. There are just too many potential new antibody-based treatments for them all to be properly evaluated in the clinic. Many will still fail because of factors that are hard to predict from experiments: unexpected toxicity, biological heterogeneity of the target disease, or lack of access to the appropriate tissue. The unfortunate reality is that clinical development of new drugs is almost entirely in the hands of the pharmaceutical industry, where many factors other than strictly scientific/clinical ones influence the decision to develop a particular product. These include the availability of patent protection, the potential size of the market, the impact of new drug regulations, and the current mood of From: Methods in Molecular Medicine, Vol. 40: Diagnostic and Therapeutic Antibodies Edited by: A. J. T. George and C. E. Urch © Humana Press Inc., Totowa, NJ
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investors. Profitability is the overriding concern and is an essential ingredient of success in our society. However, we do not think it is enough for academic scientists to patent a new technology, license it on to industry, and sit back with large upfront payments. Physicians and their patients are cut out of the decision process and become essentially commodities to be bought or discarded during the clinical trials. A better way is for scientists, physicians, patients, industry, and government to work together, each recognizing the different priorities of the other, but each contributing to the decision process. Biological therapies will be costly and they do carry risks of introducing dangerous new diseases. We all have an interest in their effective application. Here we will tell the story of CAMPATH-1, just one of many hundreds of monoclonal antibodies (mAbs) developed for therapy. It illustrates several aspects of practical development that might apply to other projects and perhaps the reader will be able to avoid the pitfalls that we encountered. CAMPATH-1 was one of the first therapeutic mA
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