Researchers have taken the HIV virus, modified it and then used it to reprogram a cancer patients white blood cells to attack and completely kill off the cancer
Imagine pitting one fatal disease against another and staging the warfare inside the body of a 6-year-old girl who was 48 hours away from total organ failure.
Now imagine you’re the parent of that child.
For one Pennsylvania family this was the reality they were facing when their doctors had no other option but to treat their daughter Emily, who was suffering from acute lymphoblastic leukemia (ALL), with genetically altered HIV.
A research team at the University of Pennsylvania and Children’s Hospital of Philadelphia, led by Dr. Carl June, had genetically engineered T cells and used them to help several adult patients in a clinical trial with chronic lymphocytic leukemia (CLL) and ALL. The T cells needed a partner to bond with to fight the cancerous B cells that plagued Emily.
Enter HIV — the virus that causes AIDS. The idea was to use the genetically engineered HIV cells to bond with the patient’s cultured T cells to seek out the cancerous B cells and destroy them.
But HIV?
“HIV is a scary thing,” acknowledged Dr. Stephan Grupp, director of Translational Research at the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia and professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. Grupp, and his team, treated Emily with the new procedure in April 2012, funded, in part, by a $16 million research grant from the Leukemia & Lymphoma Society.
Grupp explains the process: “We’re taking the property of HIV that is valuable and isolating that property. We use the virus to basically genetically engineer T cells from kids that are good at fighting viruses and potentially good at fighting cancer. The trouble is they don’t seek cancer. We try to force the T cells to seek cancer so we put the gene in the cell. Turns out the HIV-type virus is very good at inserting into genes and cells. That’s the function we want.
“The type we use has been genetically engineered and all the characteristics of the HIV that can cause disease are out of it,” Grupp said. “It can’t grow. It can’t make copies of itself. The crippled form of HIV only retains the function of putting a gene into a cell.”
Emily Whitehead, a plucky, bright girl — call her Emma, she asks — was no longer a candidate for chemotherapy or a bone marrow transplant, a standard treatment for her type of leukemia.
In early May of 2010, at age 5, she had had a clean bill of health from her pediatrician, aside from a few swollen glands everyone chalked up to a recent cold. But as the month progressed there were signs something was amiss: blood crusting at the bottom of her nose that couldn’t be explained, blood from her gums while brushing her teeth, bruising — Kari, her mother, called her husband at work when she counted 21 bruises on Emma’s body while she was in the bathtub. She developed debilitating pain in her knees, too. A family member recognized the signs.
“My sister-in-law, a nurse, called me, crying, and said, ‘You realize, Em’s symptoms can be leukemia,’ ” her father Tom Whitehead recalled. “I said, ‘You need to calm down. We’ll take her to the doctor in the morning.’ ”
Emma woke at 1 a.m. crying in pain. Her knees hurt like never before.
“From the beginning Emily had one of the roughest induction phases they had seen in years,” Whitehead said. “She started chemo on May 28 and by June 11 she’d developed necrotizing fasciitis in both legs. The surgeon said they might have to remove her left leg from the knee down.”
The surgery worked. But not before infection took hold and her wounds had to be repacked every 48 hours.
“Still, she was in remission and [we thought] maybe this is one of the toughest induction phases,” Whitehead said.
For awhile, until October 2011, Emma underwent chemotherapy and would be out playing again within hours of receiving chemo.
“She never complained through any of it. We explained from the beginning: ‘You have cancer. You are one of the strongest kids. Not all kids are strong enough but you will beat cancer.’ One day she was crying and said, ‘I’m not brave enough. I’m really scared all the time.’
“I said, ‘The biggest heroes in history were scared to death whenever they did something heroic. Don’t confuse being brave with being scared.’ From then on she didn’t complain. She said, ‘Just tell me when it’s going to hurt. Don’t lie to me,’ ” Whitehead recalled.
But the remission didn’t stick and more chemo didn’t help.
“The typical treatment is bone marrow transplant but she relapsed, got more intensive chemo, then relapsed again. From that time forward we could not get back into remission and couldn’t control it with chemo so bone marrow transplant was off the table,” Grupp said.
As Emma clung to life, doctors suggested the new treatment that had the mysterious name, Cart 19. The clinical trial, now called CTL019, uses immune T cells taken from a patient’s own blood. These T cells are genetically modified in the lab to express a protein that will bind to a target found on cancerous B cells. The engineered HIV is the agent that seems to make the process work, researchers found.
“The [HIV] virus has been engineered so it can’t cause disease anymore but retains its ability to reprogram the immune system so it will now attack cancer cells,’’ June said in a video that documents Emma’s story. “We call those modified immune cells serial killer cells. Each infused cell can kill more than 1,000 different tumor cells.”
Three adults were treated with this procedure before Emma. Two went into complete remission and have remained as such for 21/2 years. The Whiteheads decided to proceed.
“As we told her parents, Emma would be the first kid ever to get this and only the fourth person to get this,” Grupp said.
Since Emma’s procedure, 15 children have had the procedure.
“Of the first six patients we reported on in the literature, five went into complete remission, one of those had reoccurement of the disease. That’s what we are seeing in the study, an 80 percent short-term response rate. How that holds up in time we’re not in a position to say. But we’re very impressed by the short-term response rate. We will have to follow these kids,” Grupp said.
Whitehead hasn’t quite exhaled. “We’re thankful for every day but still nervous every day.”
Emma’s success wasn’t instantaneous, however. In fact, “she could not have gotten any sicker without dying,” Grupp said.
After the April procedure, Emma had an averse reaction. She couldn’t breathe on her own. Her blood pressure skyrocketed. Doctors put Emma into a coma. She was in too much pain. At one point she had 17 IV pumps keeping her alive, her father said.
After a few days on the ventilator a doctor took the Whiteheads into the hospital’s hallway to deliver the bad news. The procedure didn’t work.
“She’s not going to be here tomorrow,” they said. “Kids can’t survive this,’ ” Whitehead said.
Whitehead refused to accept the opinion. “I said, ‘I can’t tell you how I know this for sure, but she will be here tomorrow.’ ”
Then, a discovery.
All the activated T cells produced inflammatory proteins and one of the proteins — interleukin 6 (IL6) — went through the roof. Someone in the research lab hit upon an idea. June’s daughter had taken a drug to aid her rheumatoid arthritis, which is exacerbated by IL6. Maybe the treatment to reduce IL6 could be the answer.
“Turns out this particular inflammatory protein can be blocked with the drug designed to block rheumatoid arthritis,” Grupp said.
Within hours after receiving the arthritis medication, Emma began to recover.
“It was the most astonishing thing I’d ever seen,” Grupp said. “Her fever went away almost immediately. Her breathing difficulties resolved overnight. She was on three meds for her blood pressure and we couldn’t get rid of them fast enough because she didn’t need them anymore. From that point forward she’s been fine.
Today, Emma is 8 and a healthy second-grader. Her Facebook page, Prayers for Emily (Emma) Whitehead, has had more than 300,000 views so far and nearly 22,000 “likes.”
In June, Emma, clutching a bright purple stuffed animal, and her parents walked the halls of the U.S. Capitol to urge legislators to support the research that saved her life. The Whiteheads traveled to Washington, D.C., as part of Family Advocacy Day sponsored by the National Association of Children’s Hospitals.
The trials are ongoing.
“In principle, the T-cell approach might be adapted to other cancers but this type of thing only works for that kind of cancer,” Grupp said. “There’s every intent in the next six months or so to get a clinical trial that involves multiple adult and pediatric hospitals.”
Imagine pitting one fatal disease against another and staging the warfare inside the body of a 6-year-old girl who was 48 hours away from total organ failure.
 |
Click here to view the Original Image Size |
Now imagine you’re the parent of that child.
For one Pennsylvania family this was the reality they were facing when their doctors had no other option but to treat their daughter Emily, who was suffering from acute lymphoblastic leukemia (ALL), with genetically altered HIV.
A research team at the University of Pennsylvania and Children’s Hospital of Philadelphia, led by Dr. Carl June, had genetically engineered T cells and used them to help several adult patients in a clinical trial with chronic lymphocytic leukemia (CLL) and ALL. The T cells needed a partner to bond with to fight the cancerous B cells that plagued Emily.
Enter HIV — the virus that causes AIDS. The idea was to use the genetically engineered HIV cells to bond with the patient’s cultured T cells to seek out the cancerous B cells and destroy them.
But HIV?
“HIV is a scary thing,” acknowledged Dr. Stephan Grupp, director of Translational Research at the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia and professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. Grupp, and his team, treated Emily with the new procedure in April 2012, funded, in part, by a $16 million research grant from the Leukemia & Lymphoma Society.
Grupp explains the process: “We’re taking the property of HIV that is valuable and isolating that property. We use the virus to basically genetically engineer T cells from kids that are good at fighting viruses and potentially good at fighting cancer. The trouble is they don’t seek cancer. We try to force the T cells to seek cancer so we put the gene in the cell. Turns out the HIV-type virus is very good at inserting into genes and cells. That’s the function we want.
“The type we use has been genetically engineered and all the characteristics of the HIV that can cause disease are out of it,” Grupp said. “It can’t grow. It can’t make copies of itself. The crippled form of HIV only retains the function of putting a gene into a cell.”
Emily Whitehead, a plucky, bright girl — call her Emma, she asks — was no longer a candidate for chemotherapy or a bone marrow transplant, a standard treatment for her type of leukemia.
In early May of 2010, at age 5, she had had a clean bill of health from her pediatrician, aside from a few swollen glands everyone chalked up to a recent cold. But as the month progressed there were signs something was amiss: blood crusting at the bottom of her nose that couldn’t be explained, blood from her gums while brushing her teeth, bruising — Kari, her mother, called her husband at work when she counted 21 bruises on Emma’s body while she was in the bathtub. She developed debilitating pain in her knees, too. A family member recognized the signs.
“My sister-in-law, a nurse, called me, crying, and said, ‘You realize, Em’s symptoms can be leukemia,’ ” her father Tom Whitehead recalled. “I said, ‘You need to calm down. We’ll take her to the doctor in the morning.’ ”
Emma woke at 1 a.m. crying in pain. Her knees hurt like never before.
“From the beginning Emily had one of the roughest induction phases they had seen in years,” Whitehead said. “She started chemo on May 28 and by June 11 she’d developed necrotizing fasciitis in both legs. The surgeon said they might have to remove her left leg from the knee down.”
The surgery worked. But not before infection took hold and her wounds had to be repacked every 48 hours.
“Still, she was in remission and [we thought] maybe this is one of the toughest induction phases,” Whitehead said.
For awhile, until October 2011, Emma underwent chemotherapy and would be out playing again within hours of receiving chemo.
“She never complained through any of it. We explained from the beginning: ‘You have cancer. You are one of the strongest kids. Not all kids are strong enough but you will beat cancer.’ One day she was crying and said, ‘I’m not brave enough. I’m really scared all the time.’
“I said, ‘The biggest heroes in history were scared to death whenever they did something heroic. Don’t confuse being brave with being scared.’ From then on she didn’t complain. She said, ‘Just tell me when it’s going to hurt. Don’t lie to me,’ ” Whitehead recalled.
 |
Click here to view the Original Image Size |
But the remission didn’t stick and more chemo didn’t help.
“The typical treatment is bone marrow transplant but she relapsed, got more intensive chemo, then relapsed again. From that time forward we could not get back into remission and couldn’t control it with chemo so bone marrow transplant was off the table,” Grupp said.
As Emma clung to life, doctors suggested the new treatment that had the mysterious name, Cart 19. The clinical trial, now called CTL019, uses immune T cells taken from a patient’s own blood. These T cells are genetically modified in the lab to express a protein that will bind to a target found on cancerous B cells. The engineered HIV is the agent that seems to make the process work, researchers found.
“The [HIV] virus has been engineered so it can’t cause disease anymore but retains its ability to reprogram the immune system so it will now attack cancer cells,’’ June said in a video that documents Emma’s story. “We call those modified immune cells serial killer cells. Each infused cell can kill more than 1,000 different tumor cells.”
Three adults were treated with this procedure before Emma. Two went into complete remission and have remained as such for 21/2 years. The Whiteheads decided to proceed.
“As we told her parents, Emma would be the first kid ever to get this and only the fourth person to get this,” Grupp said.
Since Emma’s procedure, 15 children have had the procedure.
“Of the first six patients we reported on in the literature, five went into complete remission, one of those had reoccurement of the disease. That’s what we are seeing in the study, an 80 percent short-term response rate. How that holds up in time we’re not in a position to say. But we’re very impressed by the short-term response rate. We will have to follow these kids,” Grupp said.
Whitehead hasn’t quite exhaled. “We’re thankful for every day but still nervous every day.”
Emma’s success wasn’t instantaneous, however. In fact, “she could not have gotten any sicker without dying,” Grupp said.
After the April procedure, Emma had an averse reaction. She couldn’t breathe on her own. Her blood pressure skyrocketed. Doctors put Emma into a coma. She was in too much pain. At one point she had 17 IV pumps keeping her alive, her father said.
After a few days on the ventilator a doctor took the Whiteheads into the hospital’s hallway to deliver the bad news. The procedure didn’t work.
“She’s not going to be here tomorrow,” they said. “Kids can’t survive this,’ ” Whitehead said.
Whitehead refused to accept the opinion. “I said, ‘I can’t tell you how I know this for sure, but she will be here tomorrow.’ ”
Then, a discovery.
All the activated T cells produced inflammatory proteins and one of the proteins — interleukin 6 (IL6) — went through the roof. Someone in the research lab hit upon an idea. June’s daughter had taken a drug to aid her rheumatoid arthritis, which is exacerbated by IL6. Maybe the treatment to reduce IL6 could be the answer.
“Turns out this particular inflammatory protein can be blocked with the drug designed to block rheumatoid arthritis,” Grupp said.
Within hours after receiving the arthritis medication, Emma began to recover.
“It was the most astonishing thing I’d ever seen,” Grupp said. “Her fever went away almost immediately. Her breathing difficulties resolved overnight. She was on three meds for her blood pressure and we couldn’t get rid of them fast enough because she didn’t need them anymore. From that point forward she’s been fine.
Today, Emma is 8 and a healthy second-grader. Her Facebook page, Prayers for Emily (Emma) Whitehead, has had more than 300,000 views so far and nearly 22,000 “likes.”
In June, Emma, clutching a bright purple stuffed animal, and her parents walked the halls of the U.S. Capitol to urge legislators to support the research that saved her life. The Whiteheads traveled to Washington, D.C., as part of Family Advocacy Day sponsored by the National Association of Children’s Hospitals.
The trials are ongoing.
“In principle, the T-cell approach might be adapted to other cancers but this type of thing only works for that kind of cancer,” Grupp said. “There’s every intent in the next six months or so to get a clinical trial that involves multiple adult and pediatric hospitals.”
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