Monoclonal antibodies, clinical uses

After the approval of the first product, recombinant insulin, in 1982, progress in the development of new recombinant protein pharmaceuticals was slow ([10], Fig. 17.1). The number of biotechnology-derived drugs and vaccines approved by the US Food and Dmg Administration (FDA) has increased significantly only since 1995. More recently, sales of biologies have skyrocketed, e.g. from 900 million in 1999 to an estimated 3.5 billion in 2001 for monoclonal antibodies [11]. The annual global market for biopharmaceuticals is estimated to have increased from 12 billion US to 30 billion US in 2003 [12]. 500 candidate biopharmaceuticals are undergoing clinical evaluation and over one hundred protein-based therapeutics are in the... 

The annual R D expenditure for biopharmaceuticals is around US 19-20 billion. There are estimated to be 2500 biopharmaceuticals in the discovery phase, 900 in preclinical trials, and 1600 in clinical trials. This represents 44% of all drugs in the development phase and 27% of all drugs in both preclinical and clinical trials. The most common target is cancer and monoclonal antibodies and vaccines have the largest amount of R D activities. 

The ground-breaking development of monoclonal antibodies by Kohler and Milstein [21] initiated the development of antibody-mediated therapeutics for cancer. Because of their unique specificity, MAb were predicted to become the magic bullets in the battle against cancer. Over the last two and a half decades MAbs have moved from clone to clinic for the treatment of various malignancies. Several MAbs are currently entering clinical trials and should appear on the market in the next few years. The first MAb for cancer therapy was approved in the US in 1997. 

Between 12 and IS billion US per year are spent for analytical purposes worldwide. In this sum the analytical usage of enzymes in clinical chemistry, food and cosmetic industry, and biotechnology for the routine measurement of about 80 substances, mainly low-molecular mass metabolites but also effectors, inhibitors, and the activity of enzymes themselves, is included. A wide range of immunoassays for low-molecular mass haptens, macro-molecules, and microorganisms have been made available in recent years through the enormous progress in immunological research, especially by the preparation of monoclonal antibodies. About 1 billion immunoassays are sold per year. 

Rituximab represents the most important scientific achievement of the past decade. It was the first therapeutic antibody approved for the treatment of cancer and specifically for N H L. The current IWRC for N H L had their origin with the rituximab response criteria. Clinical development was completed in record time. Dossiers were filed simultaneously in the United States and in Europe. The US fihng utilized an electronic format (computer-aided product license application, CAPLA). These and many other achievements during clinical development served to provide tremendous impetus to the monoclonal antibody research area. The renewed enthusiasm in this area has yielded many new Mabs with activity in both hematologic malignancies and in autoimmune diseases. Several of these have been approved (e.g. herceptin, alemtuzumab, mylotarg, others) and many others are under active investigation. 

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