Janice M. Reichert on Monoclonal Antibody Cancer Therapeutics
Emerging Research Front Commentary, December 2010
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Article: Outlook - Development trends for monoclonal antibody cancer therapeutics
Authors: Reichert, JM;Valge-Archer,
VE |
Janice M. Reichert talks with ScienceWatch.com and answers a few questions about this month's Emerging Research Front paper in the field of Pharmacology & Toxicology.
Why do you think your paper is highly
cited?
The paper provides a unique overview of the clinical development of antibody treatments by the commercial sector over a 25-year period (1980-2005). During this period, the technology used to produce antibody therapeutics underwent substantial changes, with the early issues of the immunogenicity associated with mouse-derived protein sequence addressed through development of humanization and transgenic mouse platforms. Starting with rituximab's approval in 1997, more than a dozen antibody products for cancer indications have now been approved in countries across the world.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
"The ultimate goal of any cancer therapeutic development program is to provide benefit to patients. I hope my research illustrates the progress to date in the development of these important products, but also shows the need for on-going scientific advancement and investment by society in cancer research."
The approach was to compile and synthesize knowledge of over 200 antibodies that targeted tumor-associated antigens and were sponsored in clinical study by pharmaceutical and biotechnology firms. Relevant information on the molecular formats, isotypes, antigenic targets, modes of action, milestone dates, and status in the clinic for the antibody candidates was required for the analysis.
Would you summarize the significance of your paper
in layman's terms?
The message of the paper was that progress in the development of antibodies for cancer has been substantial, but that the process is difficult, time-consuming, and risky. We estimated that the rate of approval success was only 20% even for the most well-established technology (humanization). Additionally, we emphasized that there are many opportunities for improvement of the molecules, e.g., by altering the formats.
Where do you see your research leading in the
future?
My research scope will continue to expand as companies across the world explore new technologies and approaches to developing novel protein therapeutics for human use. The canonical antibody therapeutic is a bivalent, mono-specific, full-size IgG1 molecule, but many new formats, such as bispecific antibodies, human domain antibodies, non-human antibodies, and alternative protein scaffolds are entering clinical study at a steady pace. These formats comprise only about 10-15% of the total number of targeted protein therapeutics in clinical study; however, these now appear to be the way of the future.
Do you foresee any social or political
implications for your research?
The ultimate goal of any cancer therapeutic development program is to
provide benefit to patients. I hope my research illustrates the progress to
date in the development of these important products, but also shows the
need for ongoing scientific advancement and investment by society in cancer
research.
Janice M. Reichert, Ph.D.
Senior Research Fellow
Tufts Center for the Study of Drug Development
Boston, MA, USA
KEYWORDS: TECHNOLOGY EVALUATION; THERAPY; IMMUNOGENICITY; IMMUNOTHERAPY; TRASTUZUMAB; PROMISCUITY; MECHANISM; ONCOLOGY; EFFICACY; DOMAINS.