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St. Jude researchers expand the use of a rare immune cell to help patients like Jordan James thrive.
As the sun slants through the lobby of the Patient Care Center at St. Jude Children’s Research Hospital, a toddler with bright eyes and a ready smile stages an epic struggle between a stuffed, orange moose and a plastic giraffe. First the giraffe attacks; then the moose fights back. Within minutes both toys soar high into the air.
“He loves wrestling,” explains Chancelly James, as she watches her 2-year-old son, Jordan, scoop the toys off the floor and offer high fives to the lobby’s late-afternoon crowd. “Who is that?” Chancelly asks Jordan, pointing to the moose. “That’s robot,” he says, switching into the appropriate stiff-legged robot gait.
Not bad for a boy doctors had feared would die in infancy or would be profoundly disabled. “We had never had a tragedy like this in the family,” says Patricia James, Jordan’s grandmother. “We all just got together and prayed. As long as he was alive, we could deal with him not being able to see or walk or talk or whatever. We just wanted him alive.”
The first challenges surfaced in July 2007, when Jordan was less than 2 days old. Chancelly was recovering from a C-section delivery when Jordan, her only child, suffered a seizure. Within hours, both mother and child were in an ambulance speeding toward Memphis. Doctors at their Louisiana hospital had told Chancelly simply that there was something bad in Jordan’s blood and that St. Jude would take it out.
The next hurdle emerged shortly after their arrival at St. Jude. Scott Maurer, MD, a St. Jude oncology fellow, felt a bulging mass on top of Jordan’s head. Tests quickly revealed the problem. Jordan had suffered a bleed so severe that the back half of his brain—including regions responsible for vision, speech, hearing and movement—was obscured by blood. The same leukemia that threatened the newborn’s life was likely responsible for the hemorrhage and seizure.
Leukemia is a cancer of certain white blood cells. Jordan was born with a rare form of the disease known as transitional B-cell acute lymphoblastic leukemia (ALL). Normally, B cells make antibodies that help protect against bacteria, viruses and other germs. But Jordan’s B cells failed to mature properly and become fully functional. His blood stream was clogged with immature B cells, causing pressure to increase inside his blood vessels and probably triggering the bleed into his brain.
Jordan’s cancer complicated efforts to treat the hemorrhage. A neurosurgeon advised against a surgical procedure to ease the pressure inside his skull, fearing it might spread his cancer. The bleed also prompted doctors to delay the start of chemotherapy.
“It was a scary situation,” Chancelly recalls. Patricia adds, “Dr. Scott [Maurer] was trying to calm us down while telling us the truth. He and the other doctors would sit us down and tell us the possibility something would work and the possibility it wouldn’t work.”
Jordan faced long odds. Infant leukemia is rare. Of the estimated 450 cancer patients who arrive at St. Jude annually, only two or three are infants with leukemia. Under the best circumstances, Maurer says, just 15 percent of patients like Jordan are cured.
But here Jordan’s story takes another turn, this time for the better. By late summer, he was out of intensive care. Separated from family and friends, Jordan’s mother and grandmother were building a St. Jude family. With chemotherapy, Jordan’s cancer had disappeared. But doctors warned that without further treatment his leukemia would eventually return.
For patients like Jordan, doctors often recommend a procedure called a hematopoietic stem cell transplant. The treatment involves replacing the diseased stem cells in a patient’s bone marrow with cells from a healthy, matched donor. Siblings typically make the best donors because having the same parents increases the odds that two individuals will carry the same markers on their cells’ surface. Those markers help the immune system distinguish between normal cells and invaders to target for destruction. Mismatched markers raise the risk that a patient will develop a potentially fatal complication known as graft-versus-host disease.
As an only child, Jordan was not a candidate for that treatment. Instead, on February 14, 2008, he became one of the first infants with leukemia to join a St. Jude pilot study using immune cells known as natural killer, or NK, cells.
NK cells are the immune system’s warriors. The cells circulate widely in the body, armed with proteins that are capable of delivering a deadly one-two punch to viruses and cancer cells. Scientists recognized the cancer-fighting potential of NK cells more than 30 years ago, but until recently efforts to use them were hampered. There are few NK cells, and those that could be isolated from donors did not always target tumor cells. NK cells account for just 5 to 10 percent of lymphocytes, or white blood cells.
St. Jude has emerged as a leading center of research into using NK cells as a possible cancer treatment. Wing Leung, MD, PhD, director of Bone Marrow Transplantation and Cellular Therapy, is pioneering efforts to better match cancer patients like Jordan with the parent or sibling whose NK cells will provide the biggest anti-cancer punch. Meanwhile, work led by Dario Campana, MD, PhD, of Oncology and Pathology, is enhancing not only the supply of NK cells available to treat patients, but also those cells’ ability to more effectively target and kill a variety of cancer cells.
NK cells now play a role in at least four St. Jude treatment plans for children battling leukemia and sarcomas. Another St. Jude trial using NK cells is expected to open later this year. Investigators hope NK cells will extend cures by targeting cancer cells that survive chemotherapy.
“Immune therapies, including NK cells, promise to be able to treat patients who are resistant to chemotherapy because they work in a totally different way,” Campana explains. NK cells are also being tried against a variety of adult cancers, including multiple myeloma and cancers of the head and neck. Campana’s laboratory is collaborating in those efforts with centers in the United States and Japan.
His laboratory developed the patented techniques that helped fuel international interest in NK cells. The methods are designed to ensure an adequate supply of NK cells to treat patients. As a result, it now takes just one week for scientists to take donor NK cells and increase their number 100 times. Campana said the technology raises hope it might soon be possible to give patients multiple infusions of NK cells that can find and destroy cancer cells.
Campana’s team has also developed a strategy to modify donor NK cells to better target cancer cells. The resulting NK cells carry an artificial receptor on their surface. That receptor helps the NK cells recognize and link to a particular protein on the surface of the most common type of ALL cells. Once the two cells find each other, the NK cell works to destroy the leukemia cell. Campana said this research provides a platform to hone the anti-cancer properties of NK cells.
Leung has taken a different approach to developing NK cells as cancer weapons. About five years ago, he directed efforts that clarified the function of a family of genes that play a pivotal role in NK cells. Those genes carry instructions for making proteins called killer immunoglobulin-like receptors or KIRs. Carried on the surface of NK cells, KIRs help the immune cells recognize and kill cancer cells. Leung and his colleagues demonstrated the importance of checking for the KIR protein on the NK cells, instead of simply determining whether individuals carried the gene.
“NK cells are all or nothing,” Leung explains. KIR proteins help determine whether NK cells attack cancer cells or ignore them. The proteins are the basis of the NK donor selection recommendations that Leung’s laboratory produces for St. Jude and the cooperative childhood cancer research organization known as the Children’s Oncology Group.
Leung and his colleagues are working to make NK donor selection even better. They recently published evidence suggesting tiny variations in the composition of KIR proteins either enhance or diminish the NK cells’ cancer-fighting ability. Investigators are now checking to see if the differences might better predict transplant outcomes.
Jordan’s family hoped NK cells could offer a cure. Both Chancelly and Jordan’s father were screened as potential NK cell donors. Tests indicated Chancelly’s cells offered the best hope.
In a process much like a blood donation, clinicians removed stem cells from Chancelly and treated them to remove other immune cells that might attack Jordan’s healthy tissue. The stem cells were then transfused into Jordan, who had received powerful anticancer drugs to eliminate his own diseased cells. A week later, Jordan received a second infusion, this time with NK cells isolated from Chancelly’s blood. Investigators hope the combination of stem cells and NK cells will be safer and more effective than a stem cell transplant alone.
During the month following the transplant, his doctors recognized that—despite the hemorrhage he had suffered in infancy—Jordan was behaving like a healthy baby.
Maurer entered Jordan’s room a day after transplant to find the child playing patty cake.
“Jordan was smiling. He could see the person he was playing with. He could make the complex movements needed to play the game,” Maurer recalls. “It was an epiphany moment. I thought to myself: ‘This kid is going to grow up, go to school and do great things with his life.’”
Now, more than two years after his transplant, Jordan remains cancer free. His health and development are closely monitored at St. Jude. Jordan’s speech has lagged a bit, but Maurer says the toddler who loves wrestling and dancing is an example of the infant brain’s resiliency. Following the bleed, undamaged regions of Jordan’s brain took on additional tasks. That helps explain why Jordan is now busy learning his letters and has such a good time singing and banging on the piano.
“This kid broke the mold,” Maurer says. “You hear stories about patients like this, but you never think you’ll meet one. He should not have survived either the cancer or the bleed.”
Leung says Jordan exemplifies the hospital’s commitment to the dream of St. Jude founder Danny Thomas that no child should die in the dawn of life. “Jordan had all the high-risk features you don’t want in a patient,” Leung says. “But we never give up.”
Infants like Jordan are not the only cancer patients who may benefit from treatment with NK cells. Leung and his colleagues also conducted research involving 10 children with acute myeloid leukemia (AML) who received NK cells from parents. The children had completed standard therapy with anti-cancer drugs and were in remission when they received the donor NK cells. Nearly three years later, all participants remain cancer free.
An editorial that accompanied a report on this research in the Journal of Clinical Oncology praised the St. Jude approach, predicting it could have far-reaching implications for improving treatment of AML.
St. Jude oncologist Jeffrey Rubnitz, MD, PhD, says although it is too soon to credit the NK cell transplant for the continued remission of patients involved, the finding helped launch a nationwide study of NK cells as a possible alternative to stem cell transplant in some children with AML.
For Jordan’s family, St. Jude is a second home. An aunt makes an annual trip from Louisiana to Memphis to volunteer. Other relatives participated in the December marathon and 5-kilometer race held in Memphis to benefit St. Jude.
Chancelly still recalls her relief when she learned she would not have to pay for Jordan’s care. “They really do spend the funds they raise on the kids,” she says. “But I fell in love with this place when I arrived. The people at St. Jude really have a love for kids.”
Reprinted from Promise Spring 2010