That can reduce their effectiveness in treating some types of cancers (e.g, solid tumors). Third, most MAbs (because of their large size) are limited in their ability to penetrate and accumulate in tissues. Second, their large size (150–160 kDa) makes them unsuitable for most intracellular therapeutic targets, so MAbs must be delivered to patients by injection or infusion ( 7). That process can be extremely labor intensive and costly ( 6). First, their complex molecular structure (four polypeptide chains - two light and two heavy), glycosylation of heavy chains, and at least one disulfide bond in each of several immunoglobulin domains require that full-size antibodies be manufactured in eukaryotic or mammalian expression systems (e.g., CHO cells). Some Clinical Limitations of Therapeutic MAbsĪlthough MAbs are one of the biotechnology industry’s greatest commercial successes to date, they possess several characteristics that can limit their utility and clinical effectiveness ( 4, 5). Currently, ~70 chimeric and humanized MAbs and 30 fully human MAbs are in various stages of clinical development worldwide ( 2). To that point, Humira (Abbott) - one of the first fully human MAbs to be marketed as a treatment for rheumatoid arthritis and other chronic inflammatory indications (Table 1) - is one of the world’s top-selling drugs with sale projected to exceed $9.3 billion in 2012 alone ( 3). Such investments - coupled with major advances in MAb engineering technology - led to development of fully-human MAbs (molecules that contain only human antibody protein sequences).įully human MAbs generally exhibit improved therapeutic efficacy and possess fewer side effects (better safety profiles) than chimeric or humanized MAbs. The commercial success of those early products prompted huge investments by pharmaceutical and biotechnology companies in therapeutic MAb drug development. KEYWORDS: ANTIBODY FRAGMENT ANALYSIS FLOW CYTOMETRY, IMMUNOHISTOCHEMISTRY RADIOLABELING PROTEIN FUSION WHO SHOULD READ: PRODUCT DEVELOPMENT, ANALYTICAL PRODUCT FOCUS: MONOCLONAL ANTIBODIES, FRAGMENTS, AND OTHER PROTEINS Since their introduction, many of those products - including Remicade, Enbrel, and other drugs - have attained blockbuster status. The first MAbs to be commercialized in the early 2000s were chimeric MAbs (genetically engineered hybrid molecules containing murine and human sequences) and “humanized” MAbs (containing 90–95% human antibody protein sequences). Table 1: Commercialized monoclonal antibodies in the United States and European Union ()
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