Monoclonal antibody based products

At least 1000 potential biopharmaceuticals are currently being evaluated in clinical trials, although the majority of these are in early stage trials. Vaccines and monoclonal antibody-based products represent the two biggest product categories. Regulatory factors (e.g. hormones and... 

Antibodies have and likely will find additional use in transplantation-related medicine. In general, cell-mediated immunological mechanisms are responsible for mediating rejection of transplanted organs. In many instances, transplant patients must be maintained on immunosuppressive drugs (e.g. some steroids and, often, the fungal metabolite cyclosporine). However, complications may arise if a rejection episode is encountered that proves unresponsive to standard immunosuppressive therapy. Orthoclone OKT-3 was the first monoclonal antibody-based product to find application in this regard. 

Table 8.6. Monoclonal antibody based products and liposome formulations registered for cancer therapy in the USA and/or Europe.

The evaluations to determine relevant species for toxicity evaluation include various receptor binding assays and tissue cross-reactivity assessments, the later being routinely performed for monoclonal antibody based products (see Chapters 10 and 26). Species specificity can be determined using properly controlled in vitro cell-based response assays, cloning of receptors and ligands to determine compatibility, receptor-based response assays, immunoassays, genomic-based assays, and traditional biochemical-based assays as well as in vivo assessments with validated endpoints and markers for specificity. 

Monoclonal antibody-based product Bexxar Corixa/Glaxo Smith Kline CD20 cells 2003... 

Recent reviews Hst more than 400 biotechnology-based pharmaceutical formulations either registered in clinical trials or undergoing review by the regulatory agencies for the treatment of nearly 150 diseases including cancer, infectious diseases, autoimmune diseases, and AIDS/HIV (1,2). Biotechnology-based pharmaceuticals already on the markets include recombinant blood factors, recombinant hormones, cytokines, vaccines, monoclonal antibody-based products, and therapeutic enzymes. 

Tables Monoclonal/engineered antibody-based products approved for general medical use...

Monoclonal antibodies have great therapeutic potential and are being pursued both by biotechnology companies and by traditional pharmaceutical companies. A recent report indicates 376 mAb development programs (from preclinical to market), 132 mAbs in clinical development, and 23 approved mAbs (see Table 26.1). The sales figures for 2002 were 5.4 billion (up 37.5% since 2001), and this market share is expected to grow to 16.7 billion by 2008. This growth is fueled by the projected launch of 19 new antibody-based products in the time period 2004 to 2008. 

Production of antisera does not require specialized immunological techniques and cell culture facilities. Therefore it may be a simpler, faster and cheaper way than production of monoclonal antibodies (see section 3.3.). However, it must be noted that antisera-based immunoassays are sometimes less selective than monoclonal antibody-based immunoassay because of the polyclonality of antibodies in the antisera, and good antisera are not reproduced. The production of high affinity antisera may be helped by long-term immunization schedules from the mechanism of antigen-dependent B lymphocyte differentiation and selection (23). 

Chen F-C, Hsieh Y-HP (1999). Detection of pork in heat-processed meat products by monoclonal antibody-based ELISA. J. AOAC, 83(l) 79-85. 

Product formation kinetics in mammalian cells has been studied extensively for hybridomas. Most monoclonal antibodies are produced at an enhanced rate during the Gq phase of the cell cycle (8—10). A model for antibody production based on this cell cycle dependence and traditional Monod kinetics for cell growth has been proposed (11). However, it is not clear if this cell cycle dependence carries over to recombinant CHO cells. In fact it has been reported that dihydrofolate reductase, the gene for which is co-amplified with the gene for the recombinant protein in CHO cells, synthesis is associated with the S phase of the cell cycle (12). Hence it is possible that the product formation kinetics in recombinant CHO cells is different from that of hybridomas. 

Biotech products based on recombinant DNA, gene expression or hybridoma/monoclonal antibody technologies. 

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... 

Monoclonal antibodies for in vivo use Cytokines (e.g. interferons and interleukins) Therapeutic enzymes Thrombolytic agents Hormones Growth factors Additional miscellaneous proteins Blood Blood proteins (e.g. albumin and blood factors) Vaccines Cell- and tissue-based products Gene therapy products Antitoxins, venoms and antivenins Allenergic extracts... 

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