In 2006, a German biotech developed what they called a “superagonist” for CD28, a pocket on T cells that in theory could be used to stimulate their ability to fight cancer. They put it in 6 healthy volunteers, each of whom became critically ill within hours as their immune system went haywire. After that, companies backed off.
“There’s been caution that you would do anything to stimulate CD28 in a non-specific manner in humans,” explained Stephen Schoenberger, a cancer immunologist at the La Jolla Institute for Immunology.
Still, the fact remained: CD-28 was a powerful way to stimulate T cells. And 2 years ago, as Regeneron spent millions developing bispecific antibodies, they filed a patent on a method to use those bispecifics to revive that old idea.