About mAbs

In January 2009 mAbs, the first international peer-reviewed journal of its kind to focus exclusively on monoclonal antibodies, was launched. We believe that this is an excellent time to start the journal because of the increasing focus on mAbs as therapeutics. There has been a rapid increase in mAb R&D by academia, government and industry located world wide. Novel mAb therapeutics are entering clinical study by commercial sponsors at a record pace (Figure 1) that is predicted to continue well into the future. MAbs have proven successful in the clinic (Table 1). In addition, a global market has emerged for the products - several novel mAbs not yet available in the US or EU are now approved in Asia and South America.
mAbs is a multi-disciplinary journal dedicated to the art and science of mAb research and development. mAbs publishs three general types of papers, i) Original research, ii) Reviews, iii) Commentaries and perspectives. Original research papers cover all topics important in the mAb field. Reviews, commentaries and perspectives on any aspect of mAb R&D are welcome.

Journal topics include (but are not be limited to):

1. Antibody engineering, e.g., immunoconjugates, antibody fragments
2. MAb targets in the therapeutic areas of cancer, immunology, and infectious diseases
3. Preclinical studies and evaluation of mAbs, e.g., mechanism of action studies, safety and efficacy studies in animals
4. Manufacturing
5. Clinical studies
6. Regulatory review of mAbs
7. Post-approval topics, e.g., pricing, reimbursement and markets
8. Patents
9. Emerging markets for mAbs, including China and India

mAbs is currently published bimonthly, and will incrementally increase in frequency to monthly issues over several years. Each issue appears in print and online. Submissions and peer review are rapid and handled online. The average time from submission to final decision (acceptance or rejection) for the current Landes Bioscience journals is one month. Once accepted, a paper is published online within three weeks.

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

Therapeutic monoclonal antibodies (mAbs) have recently attracted significant attention from the pharmaceutical and biotechnology industries. There are multiple reasons for this interest. Innovative protein engineering can be used to design antibody molecules with decreased immunogenicity, enhanced effector functions, and improved pharmacokinetic properties. Pathways to demonstrate safety, efficacy and quality to regulatory agencies have been established. 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. As a consequence of these factors, novel mAb therapeutics are now entering clinical study at a record pace.

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 main 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 [Figure 1]. An 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

Source of Figure 1: Stefan Dübel, Technical University of Braunschweig.

The characteristic "Y" shape of antibodies is visible in atomic force microscopy (AFM) images [Figure 2]. The technique is commonly used to visualize shape, domain orientation and determine molecular dimensions. AFM imaging is also used to visualize self association of mAbs and formation of antibody-antigen complexes. To acquire the image, monoclonal human IgG antibodies were diluted in phosphate-buffered saline (PBS) and incubated on mica for 5 minutes, allowing adsorption to the surface. The excess solution was removed and replaced with PBS buffer. The sample was immediately imaged using a Digital Instruments Nanoscope III atomic force microscope.

Figure 2

Source of Figure 2: Dan Anafi, Thomas M. Dillon and Pavel V. Bondarenko, Amgen.

Using genetic engineering techniques, domains of the light and heavy chains can be combined in various ways to form antibody fragments capable of binding antigen [Figure 2]. The canonical antigen-binding fragments (Fab) are composed of variable heavy (VH), variable light (VL) and constant regions of the light (CL) and heavy chains (CH). Single chain variable fragments (scFv) are produced by linking VH and VL domains together. These fragments are extremely versatile. scFv can be dimerized via a 'zipper', but will also form dimers (diabodies) when short linkers are used. In addition, scFv can be combined with other antibody fragments, including CH and crystalizable fragments (Fc). The fragments will differ from the full-size IgG molecule in characteristics such as affinity, immunogenicity, and circulating half-life.

Figure 3

Source of Figure 3: Michael Hust, Technical University of Braunschweig.

All of the currently marketed mAbs are composed of protein chains derived from either mouse or human sources, or from a combination of both. MAbs that are derived from only mouse antibody genes are referred to as murine. Chimeric mAbs are constructed from variable regions derived from a murine source and constant regions derived from a human source. Humanized mAbs are constructed with only antigen-binding regions (also called complementarity-determining regions, or CDRs) derived from a mouse, with the remainder of the variable regions, and constant regions, derived from a human source. MAbs derived from only human antibody genes are called human [Figure 3]. Generic names for mAbs reveal their genetic origins. MAb generic names end with the suffix -mab, but the preceding one or two letters indicate the animal genetic source: o = mouse, xi = chimeric, zu = humanized, u = human. For example, tositumomab is murine, rituximab is chimeric, bevacizumab is humanized, and panitumumab is human. In general, the immunogenicity of mAbs decreases with an increase in the amount of human-derived protein sequence.

Figure 4

Source of Figure 4: Joost Bakker, Genmab.

MAbs can be designed to fulfill a variety of functions. With a cell-based target, mAbs can 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.

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.