Thursday, August 13, 2015

Interesting Work on Mabs

Monoclonal antibodies are a class of antibodies which on the one hand reflect a response to a specific antigen and on the other hand can activate the immune system to respond to the cells presenting to that antigen and have them eliminated if possible.

Back in the mid-1960s when I first came across the clinical use of antibodies what was frequently employed was gamma globulin, a massive amount of mixed IgG, immunoglobulin G, from many people and it was somewhat tried as another treatment for a variety of disorders including some cases of mumps. However the specificity of IgGs and the other immunoglobulins had not yet been ascertained.

As this identification progressed it became apparent that specificity of the antibodies could perhaps be a tool to attack certain disorders, including cancers. This then led to many examinations of ways to produce large volumes of specific antibodies. The result was the development of monoclonal antibodies. Simply this is the chimeric combination of antibodies developed to attack a specific target and a vehicle cell that had immortality to bind this product to so it became a small factory for production. From this came, after a significant amount of effort, the monoclonal antibody, and in turn the new therapeutics ending in –mab.

The work of Marks, The Lock and Key of Medicine, is an effort to tell this story. It starts with some of the early researchers in the UK who persevered to get some of the initial samples available and the ever changing dynamic of researchers and clinicians. As with so many efforts of this type, there is an ever challenging set of steps that the researchers and the clinicians go through, some winning and some losing. The early days of the late 1960s, when in the practice of medicine little was truly understood but the tools for the researchers were coming on quickly.

The author takes the reader through the many individuals and the many crises and victories as they progressed. The book focuses on the many individuals and their steps in developing MABs and the ultimate commercialization of them and their application to human therapeutics.

As we progress we have seen basically four classes of Mabs. They are: murine or mouse versions with therapeutics ending in –omab, chimeric murine and human Mabs with the ending –ximab, the humanized Mabs ending in –zumab, and finally all human Mabs ending in –umab. Mabs are now one of the arms in treating a variety of diseases from cancer to arthritis and colitis. At the same time they have become “big pharma” and the author takes the reader through this process in some detail.

Overall, the book and an excellent articulation of the people, the conflicts, the achievement, and the institutional progress. From that perspective is an excellent contribution.

On the other side it would have been more helpful to have provided some simpler introductions to Mabs and the immune system. For a well-educated reader this is an interesting tale of scientific and clinical development. It does lack a feeling of personal involvement. The description of the individuals is in my opinion quite arm’s length and unlike other works of similar genre this is a discussion of facts and events and dates.

What I especially missed was the recent explosion of applications. For example in advanced melanoma there is the use of Mabs and pathway control therapeutics such as BRAF inhibitors and MEK inhibitors. This raises the issue of how does one see a blending of these two or are they not so complementary. On the other hand there are certain cancers such a prostate cancer which may be so complex and changing at such a rapid rate that Mabs would just not work. It would have been useful for the author to have contributed some substance to the debate.

Overall, again, this is an excellent book albeit for possibly a smaller community of engaged readers.