New Immunological Insights Transforming Transplant Medicine

Posted in GUMC Stories

MARCH 28, 2014—Sixty years ago, the first successful live donor kidney transplant procedure was performed in Boston between a man and his twin brother. Since then, kidney transplants have become routine, and rapid advances in the field have paved the way for transplants of more complicated organs such as the brain, heart, lung and even intestine.

Yet tricking the body’s immune system to accept a foreign organ—without compromising its ability to fight off bacteria and other pathogens—remains the biggest challenge in transplant medicine, according to a panel of experts speaking at a Georgetown University Medical Center (GUMC) event.

Doctors Speak Out , a quarterly series that convenes experts on timely health-related topics, was held Thursday, March 20, at Georgetown on “The Miracle of Transplantation: Kidney, Liver, Bone Marrow, Intestine, Heart …”

The panel comprised Thomas Fishbein, MD , and Michael Zasloff, MD, PhD , both co-directors of the Center for Translational Transplant Medicine at GUMC, and Louis M. Weiner, MD , director of Georgetown Lombardi Comprehensive Cancer Center . Veteran medical journalist Nancy Shute, who reports for NPR among other outlets, moderated the discussion. 

Tricking Our Immune Response

Organ rejection occurs because the body’s immune system is capable of detecting—and attacking—something that doesn’t belong or because the transplanted organ rejects the recipient’s body. Transplant researchers are focused on ways to silence that natural immune response, said Fishbein, also a professor of surgery. 

“While our whole body is designed to reject that new and dangerous insult, we have to manipulate or trick that immune response in some way to allow that organ to function in the body that we put it in,” he said.

According to Zasloff, also an adjunct professor of surgery, the ideal scenario in transplant surgery would be to tamp down the recipient’s immune system but in a more targeted and specific way than is possible with currently available drugs.  

“We have very powerful drugs, but they knock the heck out of the immune system and cause a lot of collateral damage,” Zasloff said.

Two Immune Systems

Zasloff explained that the body actually has two different immune systems, each with its own army of cells and biological mechanisms that co-exist: the adaptive immune system, which fights foreign tissue, and the innate immune system, which fends off pathogens. Understanding the distinction between the two is key to fine-tuning transplant medicine, he said.

It is important to maintain the integrity of the “hard-wired” innate immune system and to respect the importance of the body’s naturally occurring microbes.

“We have come to realize that we have to live in harmony with bacteria. In some cases our normal [hygienic] practices have disturbed that,” Zasloff said.

Cancer and Immunity

Another important facet of transplant science is related to cancer; bone marrow transplants are a common treatment for patients with certain cancers such as leukemia and lymphoma. Increasingly refined bone marrow transplant techniques have dramatically changed the way these cancers are treated, according to Weiner.

“It’s an extraordinarily exciting time in bone marrow transplant. We used to give whoppingly high doses of chemotherapy. Now we need to give just enough chemotherapy to get the cancer under control, do the transplant and let the immune system do its thing,” Weiner said.

In bone marrow transplant, cancerous marrow is replaced with healthy marrow, staving off blood cancers such as leukemia as well as other diseases. Yet because finding the ideal donor match is so complicated, the ability to access and apply the latest research and conduct more sophisticated procedures is essential to overcoming immunological hurdles.

To this end, Georgetown Lombardi, the cancer center Weiner heads, has partnered with the John Theurer Cancer Center at Hackensack University Medical Center—the fourth largest bone marrow transplant program in the country—to offer the residents of the Washington region the most sophisticated techniques in bone marrow transplant.

Lessons From Cancer Cells

Cancer cells also hold valuable secrets for organ transplant scientists like Fishbein and Zasloff. Tumors are able to grow unchecked because cancer cells mysteriously trick the body into thinking they belong there, effectively shutting down the body’s normal reaction to detect and attack them.

To combat this, researchers are working to craft antibodies that can block the tumor cells’ ability to deactivate this immune response, thereby “switching off the mechanism that allows cancer cells to remain invisible,” Weiner said. 

Fishbein said solid-organ transplant researchers hope to learn more about the human immune systems from these tumor cells.

“We are looking at how cancer is so clever as to evade the immune system and manipulate it to its advantage, to harness the power that cancer has figured out and that we haven’t, and to utilize it for good and not for bad,” he said.

The ability to transplant an organ and trick the immune system to automatically accept that organ, thus achieving the state researchers refer to as “tolerance,” is the “holy grail” of transplant science for the next 10 to 15 years, Fishbein added.

By Lauren Wolkoff
GUMC Communications