The hottest segment of the biotechnology industry is the production of human monoclonal antibodies (Mabs), which are used as therapeutics in the treatment of cancer and other serious conditions. The demand for these biopharmaceuticals is reflected in global sales that jumped from $300 million in 1997 to $25 billion in 2007, with an estimated continued annual growth of 14 percent, based on the most recent economic analysis. Six of these Mabs are blockbusters, with annual sales in excess of a billion dollars per year. This strategic network addresses the desirability of modifying and controlling the production of Mabs so they have defined structures that maximize their potential for clinical use. The glycan structure attached to the Mab protein is variable, but it has been shown that this component is extremely important for biological function.
The Strategic Network for the Production of Single-type Glycoform Monoclonal Antibodies (MabNet) is led by Mike Butler (University of Manitoba) and involves 20 professors based in 9 Canadian universities in collaboration with 12 Canadian biotechnology/pharmaceutical companies and 3 government institutions.
The Strategic Network for the Production of Single-type Glycoform Monoclonal Antibodies (MabNet) aims to develop techniques to produce Mabs with single or limited structural glycan variation. This will be performed by a combination of bioanalyticals, molecular biology, biochemical engineering, molecular re-construction and downstream processing, and organized into specific theme areas. The overall objective is to develop consistent methods for the production of large quantities of single glycoform Mabs. There are several model Mabs that will be developed in the network. The lead candidate is a chimeric antibody (llama/human) that has been shown to have good tumour targeting properties and a high level of penetration of solid tumours because of its small molecular size. The network will develop novel bioprocesses for the production of these antibodies in a structural form that maximizes their functional capabilities as biopharmaceuticals.
In the manufacturing of biotherapeutic proteins there are many concerns over the quality, efficacy, cost of goods and, most importantly, the lack of unwanted side effects. Processes which better control the glycoforms of monoclonal antibodies will be valuable for other protein products in addition to Mabs. The progress of MabNet is important to Canadian biotechnology partners, as it enables a large academic group, with diverse expertise and capabilities beyond any single commercial entity's internal program, to address the downstream fine tuning of biotherapeutics. The collaborative participation of industry in the NSERC-funded MabNet project allows industry to keep abreast of cutting-edge progress in glycoform control, while at the same time maintaining ongoing commercial goals in the open market. It is anticipated that new processes and products resulting from MabNet have the potential to become, or add value to, new pipeline products.