Mission Statement

mAbs provides a forum for communication on the topic of monoclonal antibody research and development, with a focus on therapeutics. Within the last decade, these versatile molecules have attracted significant attention from academic, government, and industrial organizations world-wide. mAbs publishes relevant and timely original research, as well as authoritative overviews, commentary and perspectives providing context for the work presented in mAbs and for key results published elsewhere. The journal has a strong scientific and medical focus, but also strives to serve a broader readership. All topics related to monoclonal antibody R&D are included. The journal's content is of interest to scientists, clinical researchers, and physicians, as well as the wider mAb community including readers concerned with technology transfer, legal issues, investment, regulatory requirements and strategic planning.

Background: Monoclonal antibody therapeutics

April 16, 2008

Therapeutic monoclonal antibodies (mAbs) have recently attracted significant attention from the pharmaceutical and biotechnology industries. There are multiple reasons for this interest. From the business perspective, mAbs represent potential solutions to challenges facing the industry, including the dearth of innovative candidates in the pipeline and low approval success rates for new therapeutics. Innovative protein engineering allows for the design of antibody molecules with decreased immunogenicity, enhanced effector functions, and improved pharmacokinetic properties. Novel mAb therapeutics are entering clinical study at a record pace that is predicted to continue well into the future. Pathways to demonstrate safety, efficacy and quality to regulatory agencies have been established. As of April 2008, total of 21 mAb therapeutics have been approved in the US and other countries [Table 1], and these marketed products currently have global sales of over $20 billion.

A key feature of mAbs is the malleability of their structure and function. Most therapeutic mAbs are immunoglobulin (Ig) G, which is derived from B-cells and is the most abundant type of Ig produced by the human body. IgG has two primary functions: to bind antigen, and eliminate or inactivate the antigen. IgG is a complex molecule composed of a total of four protein chains with attached carbohydrates. A full size IgG molecule is a homodimer of two light chains, each with a variable and constant domain, and two heavy chains, each with one variable and three constant domains [Figure 1]. Using genetic engineering techniques, domains of the light and heavy chains can be combined in various ways to form antigen-binding fragments [Figure 2]. The full-size molecule and fragments can also be modified to affect antibody characteristics such as affinity, immunogenicity, and circulating half-life.

Figure 1

Figure 2

Source of Figures 1 and 2: Stefan Dübel, Technical University of Braunschweig.

MAbs can be designed to fulfill a variety of functions. With a cell-based target, mAbs can be used to target a toxin or radiolabel to a specific location. Alternatively, they can block targeted receptors or induce apoptosis. Depending on the properties of the molecules, mAbs can also work in conjunction with other immune system components and affect a target through antibody-dependent cell cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). In addition, mAbs can sequester soluble targets.

Since 1980, over 500 mAbs have entered clinical study by commercial sponsors. More than 200 are now in clinical study, and new candidates are currently entering clinical study at an average rate of 35 per year. Nearly 90% of mAb candidates are studied in three therapeutic categories: approximately 50% have been studied as cancer treatments, 25% have been studied as immunological agents and 12% have been studied for either prophylaxis or treatment of infectious diseases. Of the US-approved mAbs, nine are cancer treatments, nine are indicated for immunological indications and one is an anti-infective agent.

In the future, the versatility of mAbs will continue to serve as a strong driver of research and development (R&D) of these molecules by the pharmaceutical and biotechnology industries. The established production methods and approval pathways, along with relatively high (approximately 20%) approval success rates and competitive R&D times, have served to attract much attention. The potentially large markets will ensure continued focus on therapeutic mAbs.