Licensed from BIDMC, this test creates new opportunities for personalized effective management of renal graft patients.
A serious injury in his last high school game took Terry Strom, MD, away from football training and sidelined his dreams of a career in sports. Instead, he found himself in medical school where a riveting talk about training the immune system to protect, rather than attack, transplanted tissues set him on a new career path. It was the early 1970s and conventional immunosuppressive drugs being given to patients post-transplant not only destroyed the dangerous T-cells that were rejecting patients’ new kidneys or livers, but also destroyed the protective T-cells needed to fight infectious microbes. As a result, transplant patients were at significant risk of developing infections and even some cancers. But Strom went back to the talk he’d heard in medical school: Perhaps the immune system had the ability to control itself, and if you could tap into this feature, you could work with, rather than against, this powerful system. Strom went on to observe that immune cells express insulin receptors when activated. And this observation led to his discovery that other surface molecules, notably interleukin-2 (IL-2), were enabling the destructive T-cells to mobilize against transplanted tissue, or in the case of autoimmunity, against the patient’s own tissue. In the mid-1980s, Strom began conducting experiments showing that rodent antibodies which bind to IL-2 could prolong allograft survival. The process of “humanizing” these antibodies took several years, until, in 1992, the anti-CD25 antibody was patented by the former Beth Israel Hospital. Soon after, the patent was one of several in a portfolio licensed to a startup and later sublicensed to Novartis Pharmaceuticals and Roche. Approved by the U.S. Food and Drug Administration in 1998, Strom’s invention helps form the basis for basiliximab and daclizumab, marketed as Simulect and Zenapax. This new class of immunosuppressive agents selectively use the body’s own immune system to prevent the acute rejection that causes kidney transplants to fail, providing patients with an alternate treatment option. Safe and generally well-tolerated, the agents have proven particularly valuable for older patients and for individuals who are at higher risk of developing complications from standard immunosuppressive agents.
But better drugs don't solve all the problems. ""As humans, we're snowflakes,"" Strom says. ""What works for one person doesn't work for another."" Strom’s more recent finding that certain gene activity in immune cells provides an early warning system of rejection, and forms the basis of an important new diagnostic. The test, which came on the market in the spring of 2012, is helping doctors determine if transplant patients are at risk of rejecting new kidneys -- weeks before clinical symptoms or other standard tests can detect these events.
Organ transplant failure not only affects patient outcomes and quality of life, it also drives up healthcare costs. The median annual Medicare cost for a beneficiary whose kidney transplant failed was nearly $51,000 – an astounding 500 percent more than the cost for a beneficiary with a functioning transplant. For more than a decade, Terry Strom methodically interrogated the biological mechanisms that lead to a transplant recipient rejecting the grafted organ. In 2008, he was finally satisfied that his “panel” of biomarkers constituted the first reliable test to predict rejection. In March 2012, Strom saw his scientific pursuit reach the marketplace when Quest Diagnostics, a Fortune-500 company with headquarters in Madison, New Jersey, launched a new diagnostic based on these biomarkers. Licensed from BIDMC, the test creates new opportunities for personalized and far more effective management of renal graft patients, enabling physicians to quickly determine if patients’ immunosuppressive medications need to be adjusted to help prevent rejection.