2012-11-14 10:14:19 - Thomas Platts-Mills, Division Head of Allergy, Asthma & Immunology at the University of Virginia, will be giving a presentation entitled, “The Significance of IgE Antibodies to Galactose-alpha -1, 3-Galactose (alpha-gal)” at GTC’s 2nd Allergy & Respiratory Drug Discovery Conference taking place in San Diego, CA on January 31st – February 1st, 2013.
In 2008, Dr. Platts-Mills’ lab reported that the monoclonal antibody cetuximab (erbitux) was causing anaphylaxis on first infusion because of pre-existing IgE specific for the glycosylation (Chung et al NEJ Med 2008). In addition, they established that the IgE were specific for alpha-gal, which was produced by the mouse cell line. In 2009, they identified a novel form of anaphylaxis to red meat which was also related to IgE specific for alpha-gal (Commins et al JACI 2009). The distribution of IgE specific for alpha-gal in the USA is primarily in the South East, and an important if not the only cause of these antibodies is bites from the lone star tick Amblyommaamericanum (Commins et al JACI 2011). His lab has
identified an ecto-parasite induced IgEab response that can create a risk with the use of recombinant molecules made in mammalian cell lines. Alpha-gal on cetuximab is on the FAB portion of the heavy chain, by contrast in some other monoclonals this oligosaccharide is present on the Fc glycosylation site. Together with Dr. Parren, Dr. Platts-Mills has recently reported that this Fc site is not exposed in an intact IgG and is not capable of causing reactions (Nature Biotech, 2011). The specific problem is unlikely to occur again because i) most new MAb don’t have a glycosylation site on the FAB portion and ii) glycosylation on the Fc portion does not create a risk. However, the experience with cetuximab proves a clear warning that post-translational changes in a recombinant molecule can create a target for pre-existing IgE antibodies.
Thomas A. E. Platts-Mills, Ph.D., is the Oscar Swineford Jr. Professor of Medicine and head of the Asthma and Allergic Disease Center at the University of Virginia. Dr. Platts-Mills has carried out research in many different aspects of the role of indoor allergens in asthma.
Dr. Platts-Mills is the former president of the American Academy of Allergy Asthma and Immunology (AAAAI) and has been active in educational efforts nationally for twenty years. He has published over 300 papers and has been a member of the Editorial Board of more than 10 journals. In addition, he was a member of the Immunological Sciences Study Section for the NIH and in 2003, was chairman of the special interest study section on Asthma and Allergic disease for NIAID.
Dr. Platts-Mills has also served on the NAEPP for NHLBI. He has trained more than twenty specialists in Allergic Disease and has supervised eight PhD’s. He received his degree in Animal Physiology from Oxford University (1963) and his MD from St Thomas Hospital. In 1981 he was made a member of the Royal College of Physicians in London and became a fellow in 1982. He did his training in Allergy and Immunology with Dr. Ishizaka and Dr. Lictenstein at John Hopkins (1971-1974) and in 1983 received a PhD in Immunology from London University. He became a member of the Royal Society in 2010.
This conference is also part of the 2nd Novel Immunotherapeutics Summit, which consists of this track and three other tracks:
11th Cytokines & Inflammation
5th Immunotherapeutic & Immunomonitoring
Immunogenicity & Immunotoxicity
Over 200 leading industrial and academic experts will present at this two-day summit. The Novel Immunotherapeutics Summit will offer an in-depth examination of the challenges involved in the dynamic and ever-changing field of drug discovery and development.
For more information, please visit www.gtcbio.com/allergy