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In early results of their clinical trial, Sara Federico, MD, and her colleagues hoped to see a 20 percent improvement over national responses to neuroblastoma treatment. “More than 80 percent of children responded,” says Federico, shown here with Khushi Patel.

Immunotherapy: Power from Within

A promising new therapy mobilizes a child’s immune system to help kill cancer cells.

By Elizabeth Jane Walker
Photos by Ann-Margaret Hedges, Peter Barta

Khushi Patel with her parents

Vaishali (at left) and Chirag Patel turned to St. Jude for their daughter’s neuroblastoma treatment. As part of her therapy, Khushi receives an experimental antibody that signals the immune system to attack and kill cancer cells.

On a cold and rainy October evening last year, Chirag and Vaishali Patel discovered, to their horror, that intruders had infiltrated their happy home. Thieves had crept in, undetected, and attacked 6-year-old Khushi, a beautiful little girl whose passion for crafts was eclipsed only by adoration for her baby sister.

The invaders were, in reality, cancer cells within Khushi’s body. Their attack had been stealthy—enabling the cells to evade discovery while their numbers multiplied.

In the months before, Khushi’s tummy had hurt from time to time, but doctors had been unable to pinpoint the cause of her distress. Mild pain medicines offered only temporary relief. Finally a pediatrician detected a lump in Khushi’s abdomen. Tests not only revealed tumors on her adrenal gland, but also on her liver and lungs. Khushi had neuroblastoma, a cancer of nerve tissue, and it was spreading quickly.

It was time to evict the trespassers. Khushi’s physician sent her to St. Jude Children’s Research Hospital.

A new type of therapy

“We arrived at St. Jude on a Sunday night,” Chirag recalls. “It was pretty quiet at that time of day. But we felt some kind of spirit that we were at a good place.”

During the following weeks, that impression was confirmed as the family met Khushi’s treatment team. Chirag and his wife learned that clinicians could augment standard neuroblastoma treatment with a promising new therapy that would try to mobilize the power of Khushi’s own immune system to help destroy her cancer.

This type of therapy is called immunotherapy.

It makes perfect sense that we would try to unleash the immune system on cancer.

Sara Federico, MD


Outsmarting wily cancer cells

The chief task of our immune system is to find and eliminate viruses, bacteria, cancer cells and other foreign substances. But when healthy cells mutate to become cancerous, they may outwit our body’s natural defenses. The immune system may not recognize tumor cells as foreign or may not be strong enough to eradicate these dangerous cells.

What if we could strengthen that natural immune response? What if we could encourage the immune system to wage its own war on cancer cells?

Now we can.

“It makes perfect sense that we would try to unleash the immune system on cancer,” says Khushi’s oncologist, Sara Federico, MD. “If we can figure out how to harness it and help it attack cancer without making people too sick, we should be able to kill the cancer cells but spare the rest of the cells.”

Wayne Furman, MD

Wayne Furman, MD, and his colleagues will closely follow the children in NB2012 to find out whether the early response translates into a long-term cure.

The secret weapon

Because Khushi’s cancer was so aggressive, clinicians immediately waged an all-out assault on her disease. She enrolled in NB2012, a St. Jude clinical trial that combines standard cancer therapies—such as high-dose chemotherapy, surgery, radiation therapy and stem cell transplantation—with a secret weapon known as Hu14.18K322A. This experimental antibody, called a monoclonal antibody, is produced only at St. Jude.

The antibody used to treat Khushi’s cancer is manufactured in the Children’s GMP, LLC, an onsite facility that produces biologics and drugs under strict federal guidelines. Hu14.18K322A was engineered to decrease the pain and other side effects of antibodies used in studies elsewhere.

First, the scientists pinpointed the spot on the antibody that was causing the problems. Then they created a single point mutation designed to significantly decrease those negative side effects.

As part of the clinical trial, Khushi received the monoclonal antibody during every phase of treatment. The antibody itself does not attack the tumor cells. Instead, it alerts Khushi’s immune system to attack the cancer.

The antibody works by recognizing and binding to a protein called GD2 that is present on the surface of almost every neuroblastoma cell. By binding to GD2, the antibody signals the immune system to attack and exterminate the cancer cell.

History of an antibody

St. Jude scientists and clinicians have been studying antibody therapy for more than a decade.

In the mid-2000s, they discovered that Hu14.18K322A showed promise in children with recurrent disease or with neuroblastoma that did not respond to traditional therapy. In a subsequent study, Federico and her colleague, Wayne Furman, MD, combined that antibody with chemotherapy. They found that patients tolerated the treatment well, and that the antibody was effective against neuroblastoma.

Because of those successes, the team designed NB2012, a clinical trial for children with high-risk neuroblastoma. This time, the researchers moved the antibody therapy to the beginning of treatment, as well as throughout the second and third phases of therapy.

“We really wanted to move the bar,” Federico explains. “We didn’t want to see a 5 percent improvement over national responses to neuroblastoma treatment. We wanted to see at least a 20 percent improvement.”

After the first 20 patients completed two courses of chemotherapy and antibody therapy, Furman and Federico compared the results with those of a large national clinical trial. The St. Jude response was not 5 percent better. It wasn’t even 20 percent better.

“The early disease response was double—more than 80 percent of children responded,” Federico says. “That made us all very excited.”

Early promise

Furman recently shared the NB2012 study's preliminary results at a national scientific meeting. In 80 percent of children in NB2012, the primary tumors were 47 to 96 percent smaller. In the remaining patients, the tumors had stopped growing. “The early response is very promising, among the best that we have seen against neuroblastoma,” Furman says, “but we still have a long way to go.”

Furman, Federico and their colleagues will closely follow the children in NB2012 to find out whether the early response translates into a long-term cure. “That’s the $64 million question,” Furman says. “Now we’ve got to wait for the kids to be off therapy for two or three years.”

The first patient in the study recently passed the two-year mark, with no evidence of disease. Many other children, like Khushi, are still receiving treatment. 

Khushi Patel

Khushi Patel

In the pink

Although the first cycle of high-dose chemotherapy made Khushi extremely sick, she responded well to the rest of her treatment.

“She’s had an amazing response to therapy,” Federico observes.

Federico and other hospital staff refer to Khushi as “Sparkle,” because of her sunny personality and her affinity for brilliant pink clothing. Now 7 years old, Khushi spends her time painting, coloring, doing crafts, playing games and completing classwork through the St. Jude School Program.

“Math is my favorite thing in school,” says Khushi, who wants to pursue a medical career when she grows up. “I’d like to be a physical therapist because I could help other kids,” she explains.

Khushi’s dad says the family’s experience at St. Jude has renewed his faith in humanity.

“Out in the world, people may be fighting and killing each other, but at St. Jude people show such love,” Chirag says. “Sometimes it brings tears to my eyes when I see how the people here are willing to do everything for these kids. Our family is fortunate that St. Jude is there for us.”

As Khushi completes her last phase of treatment, her parents exude a renewed spirit of optimism and hope.

“She has come through a really rough time,” Vaishali muses. “Now we want her to enjoy life. God is great; life is good. You don’t know what is going to happen in the future, so we want her to enjoy life as much as she can.

“And we will never, ever forget what St. Jude has done for us.” 

Tagging Antibodies to Predict Treatment Response

Researchers develop radioactive tags to predict which patients can benefit from antibody therapy

Immunotherapy’s success hinges on an antibody’s ability to bind to an antigen on the surface of a cancer cell. An antigen called GD2 is present on almost all neuroblastoma and melanoma tumors. GD2 also appears on the surface of some osteosarcoma, Ewing sarcoma and small-cell lung cancer cells. 

By binding to GD2, the antibody triggers the patient’s own immune cells to spring into action.

But for some children, antibody therapy does not work well. A child’s immune system may be so weak that it cannot muster the strength to fight the tumor. Or low levels of GD2 preclude a robust immune response.

How can scientists predict which patients have enough GD2 to benefit from antibody therapy?

Scott Snyder, PhD, of St. Jude Diagnostic Imaging and Barry Shulkin, MD, Nuclear Medicine chief, have developed radioactive tags to do just that.

“The idea is that we give the child a small dose of the antibody that has this little bit of a radioactive tag on it,” Snyder explains. “Then we do a scan. If the antibody binds to the tumor, the tumor will light up on the scan. If it doesn’t light up, then we know the tumor doesn’t express GD2 and the antibody therapy isn’t likely to help that child.”

Besides creating radioactive tracers that determine GD2 expression, Snyder and his team are also developing a tag that can destroy the cancer.

“The long-term goal is to tag the antibody with a radioisotope that would actually kill the tumor cells by itself,” he says. “You’ve got the immune system that’s killing the tumors and you’ve got the radioactive tracer that’s killing even more tumors. So it should be twice as effective.”

Snyder predicts the new tracer will soon be approved for use in patients.

“It’s really exciting that tracers we developed in our cyclotron radiochemistry lab will be helping patients within the next year,” he says.


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