Humanized monoclonal antibodies Avastin

I Biologic Therapy. Bevacizumab (Avastin, rhu-MAb VEGF) is a recombinant, humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). Bevacizumab, in combination with intravenous fluorouracil-based chemotherapy, was approved by the FDA in 2004 for initial treatment of patients with... 

Chimeric or humanized monoclonal antibodies, and have the suffixes -ximab (chimeric antibodies that are about 65 percent human) or -zumab (humanized antibodies that are about 95 percent human). Getuximab (Erbitux) is a chimeric antibody that was approved by the FDA in 2004 for the treatment of colorectal, head, and neck cancers. Bevacizumab (Avastin) is a humanized antibody approved by the FDA in 2004 that shrinks tumors by preventing the growth of new blood vessels into them. 

Avastin (tradename, also known as bevacizumab) is a 149 kDa recombinant humanized monoclonal IgGl antibody first approved for medical use in the USA in 2004, and subsequently in the EU in 2005. It is indicated for first-line treatment of patients with metastatic colorectal cancer, in combination with specified (5-fluorouricil-based) small molecule chemotherapeutic drugs. 

Finally, bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody has also been approved for treatment of colorectal and breast cancer. There are several... 

The first murine monoclonal antibody was approved for marketing in 1986/ when Orthoclone (CD3-specific antibody)/ or OKT3/ was approved. NoW/ humanized antibodies/ engineered so that HAMA response is mitigated have become mainstream therapy/ with such recent successes as Raptiva/ ErbituX/ and Avastin (Table 32.1). A successful antibody also needs to be potent and specific (6). The following sections describe how engineered antibodies can be produced to meet these requirements. 

Erythropoietin has remained the best-selling human medicine for the past 3 years, followed by Lipitor (Atorvastatin), and both of these had over 12 billion in sales [20-22]. The sales of erythropoietin in Japan were over 1 billion. Tumor necrosis factor inhibitors, interferons, and insulins with, respectively, sales of 8.6 billion, 7.3 billion, and 6.5 billion in 2005 were the third, fourth, and fifth bestselling products after EPO and Lipitor (Table 1.5-8) [20-22, 24, 25]. The time taken to reach 1 billion annual sales for monoclonal antibodies has varied and was much faster for follow up and cancer products (Fig. 1.5-1). Rituxan is the leading antibody since 2003 by sales. The growth of Avastin and Erbitux has been much faster as compared to Herceptin and took only two years to reach 1 billion sales. 

Over the past decade, a wide variety of antibody-based targeting molecules have been assessed for their potential application in cancer therapy [200]. Monoclonal antibodies (mAb) were the first and are still the preferred class of targeting molecules. Current developments of antibodies have been focused on chimeric, humanized, and fully humanized derivatives to decrease their immunogenicity. Some of these antibody-based drugs have already undergone clinical development and have been successfully translated into the clinical environment. Such examples include rituximab (Rituxan ), trastuzumab (Herceptin ), cetuximab (Erbitux ), and bevacizumab (Avastin ). Rituximab was approved by the FDA for treating B-cell lymphoma in 1997. 

---