Researchers from the Antibody and Vaccine Group at the University of Southampton, England, have identified a way to repurpose antibody-based autoimmunity drugs to treat cancer. Turning on a simple molecular 'switch,' they were able to successfully use these drugs to treat cancer in preclinical trials.
CD40 is a molecule found on the surface of immune cells that is known to play a role in autoimmunity disorders and cancer. Overstimulation of the molecule increases the chance of the immune system attacking healthy cells. Meanwhile, under-stimulation allows cancerous tumor cells to sneak past the immune system and multiply. Due to its role in both diseases, CD40 is a drug target for both autoimmune and cancer treatments.
Although drugs are currently under development to either activate or suppress CD40, until recently, they were developed in isolation of each other. But his may no longer need to be the case. Researchers have found a way to invert the function of CD40 by merely modifying the 'constant' domain of different antibody treatments.
Using this inversion 'trick' in the antibody drugs, they were able to change drugs from being CD40 suppressors (for autoimmune disorders) to CD40 activators (for cancer). One, in particular, was able to stimulate the immune system to fight cancer more effectively in preclinical trials than the best CD40-targeting antibody currently in clinical trials.
"Our findings build on a history of CD40 research here in Southampton and were surprising and exciting in equal measure," said Professor Mark Cragg, senior author of the study. "Taking an antibody that suppresses the immune system and turning it on its head, to activate the immune system for cancer through a relatively simple process is unprecedented. More than that, the same approach could be used for other immune targets and we look forward to seeing testing this in the near future".