Shark Week, Day 3: An Antibody for Everybody?
There has always been something shark-like about John McCain. Unpredictable, irrepressible, and seemingly never at rest, the 80-year-old Arizona Republican is arguably the hammerhead of the U.S. Senate. And yesterday, it was fun to see those powerful chompers at work on his fellow lawmakers. In a fiery oration on the senate floor, the five-foot-nine-inch vertebrate implored his colleagues to stiffen their spines against pressure from the White House—declaring, “We are not the president’s subordinates, we are his equals!”
That he did this just a week and a half after a delicate surgery to remove a blood clot along with cancerous tissue in his brain is, well, vintage McCain. It was one more reminder of how tough the guy—who survived years in captivity as a prisoner of war and an earlier bout with melanoma—truly is.
The cancer McCain is now fighting, glioblastoma multiforme (or GBM), is brutal and aggressive, and the standard treatments in the clinic (surgery, radiation, and chemotherapy—typically with a drug called temozolomide) haven’t moved the needle much in terms of patient survival.
There are a number of reasons why GBM is so damn hard to treat, and I won’t go into them here. But one big challenge is structural: the blood-brain barrier (BBB). The BBB isn’t quite an anatomical wall, as many assume it to be, but rather a phalanx of tightly meshed cells and protein complexes. The net effect, however, is the same: The BBB restricts certain substances, including many larger molecules (such as the drug temozolomide), from passing into the brain from the bloodstream.
To get around this gatekeeper, researchers have tried a number of approaches—including attaching drugs to nanoparticles that might slip through the BBB. But another approach, serendipitously, hails from sharks. It turns out that these long-lived fishes, who are our ancient evolutionary cousins, share the core of an adaptive immune system with human beings.
Both sharks and humans make antibodies to invading antigens—with one key difference: Human antibodies are shaped a bit like a serving fork, with one prong being the so-called heavy chain, and the other the light chain. Shark antibodies have just the heavy chain, with an antigen-grabbing domain called a VNAR at the tip. VNARs, moreover, are small and soluble…and can pass through the blood-brain barrier. That makes them a possibly effective vehicle for ferrying drugs into the brain—a potential boon for the treatment of Alzheimer’s, Parkinson’s, other disorders, and cancers of the brain and central nervous system.
One biotech firm, Ossianix, is already hard at work developing a VNAR-based drug-delivery system, in collaboration with the global pharmaceutical company Lundbeck, which focuses on drugs for brain disorders. While we are still several years away, perhaps, from a suite of shark-antibody-connected drugs in the clinic, it’s a promising area for development.
More news on the GBM front: Tomorrow (Thursday) and Friday, the Parker Institute for Cancer Immunotherapy, is hosting a glioblastoma immuno-oncology research summit in Los Angeles—bringing together top industry and academic scientists to share their research.
So keep swimming, everyone. There’s hope for all of us shark cousins.
This essay appears in today’s edition of the Fortune Brainstorm Health Daily. Get it delivered straight to your inbox.