Rewriting Immunity's Rules: New Strategies Against Cancer
When patients battle cancer, their immune system is their front line of defense, with chemotherapy and radiation treatments as extra ammunition. Many times, that combination will prove successful, but sometimes the enemy returns―and it becomes clear that the immune system needs more help.
The BMT program hosts an annual reunion for its patients; this group, photographed at this year's gathering, represents some of those who've had their transplants 10 years.
At Stanford, patients now have the option of a special kind of transplant for an exhausted immune system, a version of a whole system do-over first accomplished in 1956 by replacing a patient’s diseased bone marrow with healthy marrow from his identical twin. The bone marrow is where the body generates cells for the immune system. Over the decades, the transplant technique has been improved to make transplants possible between unrelated people. But the underlying challenge has remained the same: to provide a new immune system that recognizes the abnormality of cancer cells and destroys them while accepting the cells in its new body, just if they were original equipment.
Stanford’s protocol is called, for short, TLI/ATG. The letters represent a two-part approach to manipulating the behavior of the immune system. The regimen is based on a discovery made by Stanford immunologist Samuel Strober, MD.
The TLI/ATG strategy, initially developed through animal studies, relies on the impact of radiation on certain cells in the immune system. Strober observed that those cells could be manipulated with radiation to increase in number and to do a better job of attacking cancer cells. The other trick in the strategy is to reduce the reaction of the transplanted immune cells to their new environment. Typically, they would attack, in a behavior called graft versus host disease, but the TLI/ATG protocol suppresses that response.
“It’s a wonderful example of bench to bedside research,” said Robert Lowsky, MD, who worked with Strober, Judy Shizuru, MD, PhD, and other Stanford physicians to perfect the treatment they first saw work with mice in 2001.
Cellular transplants began at Stanford in 1986, with a bone marrow transplant for a child with leukemia. Since then, more than 3,800 adults and children have been treated. The program, with a 22-bed adult inpatient unit at the Hospital and 56-bed/chair outpatient infusion area, is recognized by the National Cancer Institute for its excellence in care and research.
Scientific advances pushed a change in the program’s name from “Bone Marrow” to “Blood and Marrow.” The staff now includes a cadre of more than 50 nurses specially certified in oncology and chemotherapy. Some have been with the program since its inception. The program also includes collaborative care rooms so patients with cardiac issues can receive that extra layer of required attention.
This treatment protocol allows patients to be physically conditioned and then transplanted almost completely without hospitalization, in comparison to the weeks of isolation behind double doors that some transplant patients must endure. But the treatment still requires juggling a complex set of interconnected events designed to push patients' immune systems down to zero while keeping them from becoming infected.
Future patients will benefit from work that continues to modulate treatment even further so those immune system cells can be even more precisely controlled, said Robert Negrin, MD, Chief of the Division of Blood and Marrow Transplantation. “There’s a lot going on now to try to understand and figure out what controls the induction of an immune response―how these cell populations talk to each other.” Then comes the issue of how to use that knowledge to predict an individual’s unique interaction to chemotherapy, radiation and transplanted donor cells.
The TLI/ATG protocol produces such a long-lasting impact on the immune system that some patients do not need additional daily medication to suppress their immune system.
The hope, Lowsky said, is to be able to manipulate the immune system to accept any donated cell or tissue, enabling any patient to have a transplant that would not trigger rejection.
About Stanford Hospital & Clinics
Stanford Hospital & Clinics is known worldwide for advanced treatment of complex disorders in areas such as cardiovascular care, cancer treatment, neurosciences, surgery, and organ transplants. Consistently ranked among the top institutions in the U.S. News & World Report annual list of "America's Best Hospitals," Stanford Hospital & Clinics is internationally recognized for translating medical breakthroughs into the care of patients. It is part of the Stanford University Medical Center, along with the Stanford University School of Medicine and Lucile Packard Children’s Hospital at Stanford. For more information, visit http://stanfordmedicine.org.