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“They told me that my T cells were actually the best T cells they’ve ever seen.”
Early in September 2013, 20-year-old Milton Wright was walking home from a modeling photo shoot when he took a bad spill, landing hard on his ribs. He expected to be sore and have bruises the next day, but was surprised when he woke up and could barely move.
Milton hobbled to the ER of Seattle Children’s Hospital, where doctors told him he was badly anemic. After reviewing his medical history, they also recommended he have a lumbar puncture, or spinal tap.
Milton knew the spinal tap was a bad sign. A two-time leukemia survivor, he was all too familiar with the procedure, designed to check the spinal fluid for the presence of cancer cells. He wasn’t really surprised when the results came back positive: the acute lymphoblastic leukemia (ALL), which he first had when he was 8 and then again when he was 14, had come back for a third time.
“I was waiting for them to give me my six months,” says Milton, keenly aware of his odds.
But Milton’s doctor, Rebecca Gardner, M.D., had something quite different to say. She recommended that Milton enter a clinical trial of a new immunotherapy called CAR T cell therapy. In this approach, T cells are extracted from the blood, engineered in the lab to recognize leukemia cells, and then given back to the patient as an infusion. The idea is that the engineered T cells will go after and kill cancer cells hiding in the body.
The approach had only been used once before at Seattle Children’s, on a 23-year-old woman with ALL. But it worked extremely well for that patient. And Dr. Gardner was hopeful it would work for Milton, too.
T cells are the cells of the immune system that recognize infected and cancerous cells and launch an attack. The engineered T cells used in Milton’s treatment are called chimeric antigen receptor (CAR) T cells because they contain a receptor that is not normally found in T cells. (In Greek mythology, a chimera is an animal that is part lion, part goat, and part snake.) The receptor recognizes a protein on leukemia cells called CD19. When a CAR T cell bumps into a cancer cell sporting the CD19 protein, it punches holes in it and destroys it on contact.
The CAR T approach is part of a larger family of immunotherapies called adoptive T cell therapy, which was pioneered in this country by Cancer Research Institute (CRI) scientific advisor Philip Greenberg, M.D.
At Seattle Children’s, where Milton was treated, the person heading up the T cell program is Michael Jensen, M.D., director of the Ben Towne Center for Childhood Cancer Research. Jensen trained under Greenberg and is now spearheading the approach in pediatric and young adult patients.
The trial that Milton was on starts with one month of chemo to kill off as many cancer cells as possible. Then the engineered T cells are administered to, in effect, clean up the job.
For Milton, the best part about the experimental treatment was the brevity. “I was sold when she told me it would only take six months,” he says. This is compared to having yet another brutal three-year course of chemotherapy, which would only be a stalling tactic anyway, since the cancer would almost certainly return.
The actual experience of receiving the T cells was, according to Milton, “the most boring-est thing ever. It was like getting an eight minute saline drip,” he says. “Then I had to stay in the clinic for 10-12 hours just to make sure I didn't have a reaction to it, and I was fine.”
At first, when Milton received the T cells, his body’s response was so mild that his doctors weren’t even sure the treatment was working. Normally, patients have some side effects, like fever and chills, which indicate that an immune response is taking hold. But Milton had none of these signs the whole first week.
“They were like, ‘Just cough, just breathe wrong, just do something to show us it's working,’” Milton says.
And then, without much warning, Milton’s condition changed. His fever spiked and his blood pressure dropped precipitously. They admitted him to the ICU, where he spent four anxious days, his doctors and nurses watching him closely.
Because the immune system is so powerful, it can easily turn from being an ally in the fight against cancer to a dangerous, unpredictable enemy. Add in the fact that the therapy involves sending an army of angry T cells into the blood all at once and the battle has the potential to get out of control. Experts refer to this toxic commotion as a “cytokine storm.”
It was to deal with precisely this danger that a CRI postdoctoral researcher on Jansen’s team, Allison De Wispelaere, Ph.D., spent several years developing a “kill switch” on the T cells that, when activated, would cause them to stand down.
The kill switch can be a lifesaver, but it is also a last resort, since it basically amounts to aborting the mission.
When Milton was in the ICU, his doctors worried that the T cells were putting too much strain on his body, and they were ready to hit the kill switch. But Milton desperately wanted to avoid that option. He knew it would squelch his one remaining hope for a cure.
I told them, ‘No, I don't want you guys to get rid of them just yet.’”
The doctors listened, and three days later Milton’s blood pressure stabilized and his fever came down. They moved him out of the ICU and back to the regular floor.
Milton’s response may have been so dramatic in part because of the quality of his T cells. “They told me that my T cells were actually the best T cells they've ever seen.”
In the weeks after receiving the infusion, the percentage of cancer cells in Milton’s bone marrow dropped to zero. He was deemed to be in remission.
As an added precaution, a few months later, Milton decided to have a bone marrow transplant, in which his bone marrow would be destroyed and then replaced with bone marrow from a matching donor. “They explained that a bone marrow transplant can up your chances of never getting it again and that's really what I'm all about.”
Realistic but Hopeful
When Milton was diagnosed with ALL the first time, at eight years old, he was not really equipped to understand the gravity of the situation. “As a kid, you know you can die from it, but I would say you don't really grasp the whole meaning of death. It wasn't something that really scared me too much when I was younger.”
Now, he says, he faces his fear with a blend of realism and hope. “You kind of have to accept your death, in a way. It probably sounds weird or cold-blooded or something like that, but I've talked to other cancer patients that have survived and I know they feel the same.”
Originally, Milton’s goal in life was to attend college, play football, and then enter the military. He had even started filling out the papers to join the Marines when he learned that the chemo he received previously had damaged his heart and made him ineligible. Fortunately, a modeling scout had seen him shopping in a clothing store and offered him a chance to model professionally, which gave him another option. He has since appeared in ads for Adidas, Zumiez, and Nordstrom.
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