Wednesday, January 13, 2016

The Longest War

From President Obama's State of the Union address, an uncontroversial goal:
For the loved ones we’ve all lost, for the families that we can still save, let’s make America the country that cures cancer once and for all.
In its 45th year, the War on Cancer is the longest "war" America has ever fought, and victory may seem to be as elusive as when it started. It is difficult, however, for us non-scientists to appreciate fully the significant advances that have been made across multiple disciplines to combat this fearsome enemy.

A cancer diagnosis was a nearly automatic death sentence a few years ago. Today improved drugs and radiation treatments, early detection, and lifestyle changes have all factored into longer survival rates and a decline in cancer deaths. Still, about 600,000 Americans die each year from the dread disease.

Tumours inhibit the maturation of dendritic cells that activate
the immune system (Center for Colorectal Disease image)
One example of the creative thinking in a war that's being waged on many fronts: Stanford researcher Edgar Engleman wondered why the dendritic cells that are part of the body's immune system don't react to cancer. [bold added]
when cancer is present, the dendritic cells act as if they were asleep at the wheel, he says: They don’t respond to the antibody signal to engulf and metabolize the tumor, they don’t present the tumor antigens to the T-cells, and so the T-cells don’t mobilize.

So to counter the soporific effect of the cancer, Engleman gave the dendritic cells a “wake-up” jolt, in the form of substances known to stimulate them, as an adjunct to the antibodies. The result was astounding. “When we gave the two things at the same time, BOOM, then we got an explosive antitumor immune response that cured the tumors in the mice. Reproducibly, over and over again.

Not only did the combination injection kill the primary tumor, but it wiped out distant metastases as well. That’s huge because, as any oncologist will tell you, in most cancers it’s the metastases that are deadly. Moreover, there was no autoimmune reaction, no toxicity, no collateral damage whatsoever. The results were published last spring in the prestigious journal Nature.

Because the antibodies are present in all healthy individuals (albeit in varying concentrations) and the stimulant substances are commercially available, in theory the approach should be eminently scalable.
The process of shepherding Dr. Engleman's idea through clinical studies and the FDA will take years and millions of dollars, not to mention locating a drug company that will view his approach as a worthy investment versus others in the pipeline.

Declaring war is easy. Actually winning it is very, very hard.

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