A small lesson for alternative medicine in the TGN1412 tragedy

By now, you've probably already heard about the young, previously healthy British volunteers for a Phase I clinical trial now fighting for their lives after receiving a monoclonal antibody therapeutic, TeGenero's TGN1412. New Scientist has a concise overview, but I also refer you to Insider at PharmaGossip Derek Lowe's In the Pipeline and Anthony Cox's excellent Blacktriangle for viewpoints from three different disciplines.

Fiddling with the immune system is tricky business, and even highly experienced scientists are having difficulties understanding the intended use of TGN1412 in autoimmune disorders like rheumatoid arthritis and "cancer-related immune deficiencies" [from TeGenero's website].

As I understand it, the antibody therapeutic was designed to bind the CD28 receptor on regulatory T cells and act as a superagonist, overriding the body's normal requirement for a second, antigen-specific signal to activate the T cells. This nonspecific, super "immune boosting" effect (ever heard of that term before?) has now put two of six volunteers into multiple organ failure.

I'm reminded of the "immune system boosting" claims of many alternative therapy hucksters. Even if such a remedy existed, the immune system is far too complex to regulate with a single, myopic approach due to its multiple checks and balances, feedback loops, and other regulatory process that normally keep us from attacking our own tissue while recognizing and mounting responses against invading organisms. Even the most clever cancer immunologists have only made incremental headway in harnessing immune responses to treat cancer.

However, alternative therapy advocates prey on the public's misunderstanding of the immune system - it's a struggle for many scientists to understand, just like how homeopaths throw around terms from quantum physics. I'm reminded of my brush with fame on an AM radio talk show a few years ago where a woman who was taking Echinacea noted that her rheumatoid arthritis got worse everyone she took the herb. My simple response was that even if Echinacea was "immune boosting," the non-specific release of cytokines could make autoimmune disorders like RA much worse. (Recent data are indeed suggestive that some Echinacea compounds may indeed have potent immunomodulatory effects.). The same goes for asthma and why I always worry about folks using Echinacea supplements whose asthma has a strong immmune component. Fortunately, most Echinacea products on the market are of such inferior quality that they only occasionally pose a threat.

But the next time some CAM huckster tries to sell you a remedy that will "boost your immune system," ask them how they can be certain you won't end up in the hospital like the unfortunate Phase I volunteers in London.