Tuesday, October 6, 2015

"Human trials" in oral [antigen] tolerance by Susan Quinn

I was trying to get hold of this book for some time and in the end I found it at Open Library. I was interested to read it once I realized that it described a biotech company, then called Autoimmune Inc.,[now no longer existing], that have tried an "oral tolerance" approach to treat autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA).   

Now, this book was published in 2001. By that time, Autoimmune had conducted two major trials, one in MS, and another in RA, and both of these phase III trials failed. As book described, the main reason for those "failures" was unusually high placebo effect.

Book itself is an interview-observation type of work. It focus is people involved in oral tolerance trials. Its main character is Howard Weiner, a neurologist at Harvard Medical School, whose lab provided the scientific basis for oral tolerance trials. 

Oral tolerance is a classical immunological phenomenon. Basically, it postulates that orally taken antigens induce special type of immune response that can cross-inhibit inflammatory immune response. So, the idea was that if patient with autoimmune disease takes target [MS or RA] antigens by oral route, then these antigens will induce special population of T cells which in turn would inhibit disease causing inflammatory T cells.

Today we know that there are several types of regulatory T cells (such as Foxp3+ T cells, IL-10+ or TGFβ1+ Tr1 cells) that can be induced by oral antigens. However, even today, after 15 years, we still have no clear understanding of exact mechanisms responsible for oral tolerance effect.

The story in this book is a prime example of difference between [bio]chemical and purely biological [drug] approaches. Biological approaches, such as oral tolerance, adoptive T cell therapies, are more complex because they involve live cells whose functionalities are not completely understood and they still store lots of unexpected surprises.

posted by David Usharauli

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