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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
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`https://www.nytimes.com/2016/08/02/health/cancer-cell-therapy-immune-system.html
`
`Setting the Bodyʼs ʻSerial Killersʼ Loose on Cancer
`After a long, intense pursuit, researchers are close to bringing to market a daring new treatment: cell therapy that turbocharges the
`immune system to fight cancer.
`
`By Andrew Pollack
`Aug. 1, 2016
`
`BETHESDA, Md. — The young surgeon was mystified. A fist-size tumor had been removed from the stomach of his patient 12 years
`earlier, but his doctors had not been able to cut out many smaller growths in his liver. The cancer should have killed him, yet here he lay on
`the table for a routine gallbladder operation.
`
`The surgeon, Dr. Steven A. Rosenberg, examined the man’s abdominal cavity, sifting his liver in his fingers, feeling for hard, dense tumors
`— but he could find no trace of cancer.
`
`It was 1968. Dr. Rosenberg had a hunch he had just witnessed an extraordinary case in which a patient’s immune system had vanquished
`cancer. Hoping there was an elixir in the man’s blood, Dr. Rosenberg got permission to transfuse some of it into a patient dying of stomach
`cancer. The effort failed. But it was the beginning of a lifelong quest.
`
`“Something began to burn in me,” he would write later, “something that has never gone out.”
`
`Half a century later, Dr. Rosenberg, who turns 76 on Tuesday and is chief of surgery at the National Cancer Institute here, is part of a small
`fraternity of researchers who have doggedly pursued a dream — turbocharging the body’s immune system so that more cancer patients
`can experience recoveries like his long-ago patient’s.
`
`Dr. Rosenberg, Dr. Carl H. June of the University of Pennsylvania and Dr. Michel Sadelain of Memorial Sloan Kettering Cancer Center
`have been at the forefront of this research for decades, laboring in separate labs in an intense sometimes-cooperative, sometimes-
`competitive pursuit to bring to fruition a daring therapy that few colleagues believed would work. Now, versions of the therapy for a
`limited number of blood cancers are nearing approval by federal regulators, and could reach the market as early as next year.
`
`The technique, known as cell therapy, gives each patient an individualized and souped-up version of their own immune system, one that
`“works better than nature made it,” as Dr. June puts it.
`
`The patient’s T-cells, the soldiers of the immune system, are extracted from the patient’s blood, then genetically engineered to recognize
`and destroy cancer. The redesigned cells are multiplied in the laboratory, and millions or billions of them are put back into the patient’s
`bloodstream, set loose like a vast army of tumor assassins.
`
`This is an unusual pharmaceutical — a drug that is alive and can multiply once inside the body. Dr. June calls these cells “serial killers.” A
`single one can destroy up to 100,000 cancer cells.
`
`The killer cells are genetically engineered to produce a complex protein, an amalgam of pieces from different parts of the immune system
`that is unlike anything seen before.
`
`“I call it a Frankenstein-like molecule,” said Dr. Renier J. Brentjens, the director of cellular therapeutics at Memorial Sloan Kettering
`Cancer Center.
`
`This radical, science-fictionlike therapy differs sharply from the more established type of immunotherapy, developed by other researchers.
`Those off-the-shelf drugs, known as checkpoint inhibitors, release a molecular brake on the immune system, freeing it to fight the cancer
`much as it fights infections by bacteria or viruses.
`
`Cell therapy, in contrast, is brewed specially for each patient, one of the many challenges the field faces in broadening its use. So far, the
`number of patients treated with cell therapy is in the hundreds, not thousands. And for now it works only for certain types of blood
`cancers, not common malignancies like breast and lung cancer. Researchers are also still working out how to control potentially lethal side
`effects. Just recently, a clinical trial was briefly halted after three patients died of brain swelling.
`
`Still, cell therapy has produced complete remissions in some patients who were out of treatment options, stirring excitement among
`doctors and patients and setting off a race among companies to bring the treatments to market.
`
`Getting to this point has taken decades of painstaking work, with many false starts and setbacks.
`
`“It was conceivable we were pursuing a ghost,” Dr. Rosenberg recalled.
`Patient No. 67
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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
`
`The son of Orthodox Jews who immigrated from Poland to New York and ran luncheonettes, Steven Rosenberg was about 6 years old
`when his family learned that many relatives, including six of his father’s nine siblings, had been murdered in the Holocaust.
`
`“I saw so much evil in the world that early on I decided I wanted to do something that would help people, not hurt people,” he said in an
`interview here. He received a medical degree from Johns Hopkins and a doctorate in biophysics from Harvard.
`
`From the start, he was a workaholic. At one point he tried to call off his relationship with Alice O’Connell, whom he would later marry,
`because he was afraid it would distract him from research.
`
`“I loved the night,” Dr. Rosenberg wrote in his book, “The Transformed Cell,” published in 1992. “I remember the exhilaration of working
`through the night in the lab, drinking thick pasty coffee that had been on the burner for hours, walking out into the sunrise.” He added: “To
`be alone and out on the edge like that, there was no feeling like it in the world.”
`
`When Dr. Rosenberg arrived at the National Cancer Institute in 1974, his first attempt at immunotherapy was to give patients T-cells
`harvested from pigs. That failed.
`
`He then began giving patients interleukin-2, or IL-2, a protein made by the body that spurs T-cells to proliferate. In some cases he treated
`patients with their own white blood cells that had been incubated in IL-2. The treatments sometimes set off such a violent immune system
`reaction that patients had to be placed in intensive care.
`
`From 1980 to 1984, he treated 66 patients without success. Then, in late 1984, he encountered patient No. 67, Linda Taylor, a Navy officer
`with melanoma whose personnel file carried the stamp “death imminent.”
`
`Ms. Taylor is still alive; her case and others catapulted Dr. Rosenberg and IL-2 onto the cover of Newsweek and the front pages of
`newspapers. Some of his colleagues at the National Cancer Institute began referring to him as Stevie Wonder, thinking he had developed a
`swelled head.
`
`But IL-2’s vaunted prowess fizzled, helping only a few percent of patients with melanoma or kidney cancer.
`
`Dr. Rosenberg then tried to surgically remove tumors and extract the T-cells that had already penetrated them, so-called tumor-infiltrating
`lymphocytes. He multiplied those cells in the lab and infused them back in the patient, along with shots of IL-2. He limited his focus to
`melanoma, the skin cancer that seemed most susceptible to immune attack.
`
`The treatment eventually achieved remissions in about 10 percent to 25 percent of patients. But it was labor-intensive and its application
`to other cancers unclear.
`
`There had to be a better way. Indeed, one approach was taking shape across the street from Dr. Rosenberg, at the Naval Medical Research
`Institute in Bethesda.
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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
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`Dr. Carl June devoted himself to creating cell therapies for cancer after his wife died of the disease. Jesse Dittmar for The New York Times
`
`Research Turns Personal
`
`The Navy was not Carl June’s desired career choice. Accepted at Stanford in 1971, he instead chose the Naval Academy to avoid the draft
`and Vietnam. The Navy sent him to medical school and for training in bone-marrow transplantation, geared toward treating people
`irradiated by nuclear weapons.
`
`When the Cold War ended, the Navy lost interest.
`
`Dr. June turned to working with T-cells at the Naval Medical Research Institute in the mid-1980s. He and a colleague, Dr. Bruce Levine,
`found a way to multiply T-cells in huge numbers outside the body, a method still used today. And in the mid-1990s, working with Cell
`Genesys, a gene therapy company, Dr. June began trying to genetically modify patients’ T-cells to kill H.I.V., the virus that causes AIDS.
`
`But when his wife, Cindy, the mother of the couple’s three children, developed ovarian cancer in 1996, Dr. June’s research turned personal.
`
`Dr. June had tried everything to save her, including the primitive immune therapies under development. But Ms. June died in 2001.
`
`“A lot of other scientists would have been disillusioned by the failure, in his case the personal tragedy,” said Sean Parker, the internet
`billionaire who is funding some of Dr. June’s work.
`
`Instead, Dr. June, who had moved to the University of Pennsylvania, stopped treating patients, and devoted himself to creating cell
`therapies for cancer.
`
`“Things that were back burner on cell therapy became front burner,” he said.
`
`Following a ʻPipe Dreamʼ
`
`In the 1980s, scientists began experimenting with gene therapy, putting new genes into cells of the body to treat disease. Michel Sadelain,
`while still a graduate student studying immunology at the University of Alberta, told colleagues that he thought the technique could be
`used to supercharge T-cells to fight cancer.
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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
`
`“At the time it sounded very pipe dream,” said Douglas Green, who was one of Dr. Sadelain’s doctoral thesis advisers and is now chairman
`of immunology at St. Jude Children’s Research Hospital.
`
`But Dr. Sadelain, he continued, “believed in his approach and he pursued it relentlessly.”
`
`After earning his Ph.D., Dr. Sadelain headed for the Whitehead Institute for Biomedical Research in Cambridge, Mass., to learn how to do
`gene therapy, using disabled viruses that could not cause disease to deliver genes into cells. By 1992, he had demonstrated that he could
`genetically engineer mouse T-cells.
`
`He then moved to Sloan Kettering. In 2003, he and his colleagues — including his partner and now wife, Isabelle Rivière — showed that
`genetically engineered T-cells could eradicate certain cancers in mice.
`
`How is this done? To fight cancer, T-cells have to recognize cancerous cells.
`
`Each T-cell in the body has unique receptors, sort of like claws that jut out from its surface. T-cells patrol the body looking for protein
`fragments that indicate a cell might be infected by a bacterium or virus. If one of its claws latches on to such a fragment, the T-cell
`destroys the cell displaying it.
`
`But cancer cells are mutated versions of the body’s own cells, not outsiders. T-cells do not always recognize them as something to kill.
`
`Early in his career, Dr. Michel Sadelain came to think that gene therapy could be used to alter T-cells to fight cancer. An adviser recalled that he “believed in his approach,
`and he pursued it relentlessly.” Jesse Dittmar for The New York Times
`
`So scientists like Dr. Sadelain decided to put a new claw on the T-cells, one that could recognize cancer by latching on to a telltale protein
`on cancer cells.
`
`The new claws came from another part of the immune system known as antibodies. Drug companies already knew how to make
`antibodies with claws that bind to specific proteins in the body.
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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
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`But the claw was not enough. Once a claw binds to a target protein, it needs a molecule to signal the T-cell to go into killing mode. Yet
`another signal helps sustain the killing. The DNA instructions for all three components are inserted into the patient’s T-cells.
`
`Since this concoction is part antibody and part T-cell, it is a chimera, like the monster of Greek mythology that is part lion, part goat and
`part serpent. The claw is called a receptor and the protein it binds to on the cancer cell, the target, is called an antigen. So the whole
`construct is called a chimeric antigen receptor, or CAR, and the use of it to treat cancer is called CAR T-cell therapy, or CAR-T.
`
`Dr. Sadelain was not alone in this work. Zelig Eshhar, an Israeli scientist, is credited with developing one of the first crude CARs around
`1989. Dr. Rosenberg, always on the lookout for new types of immunotherapy, invited Dr. Eshhar to be a visiting scientist in his laboratory
`at the National Cancer Institute.
`
`Another early developer was Dr. Dario Campana of St. Jude Children’s Research Hospital.
`
`As scientists worked to perfect the formula in the 1990s and early 2000s, there was quite a bit of sharing. Cancer cell therapy was still
`mostly an academic exercise; it was highly uncertain whether it would ever really work.
`
`Dr. June, after hearing a presentation by Dr. Campana at a conference in 2003, requested a sample of Dr. Campana’s CAR. Dr. Sadelain
`shared his design with both Dr. June and Dr. Rosenberg. The most prominent CAR developed at the National Cancer Institute owes a lot to
`Dr. Sadelain, Dr. Rosenberg said.
`
`But the science proved difficult and the research money scarce. Pharmaceutical companies showed little interest, preferring mass-
`produced drugs, one size fits all, rather than a treatment that would be made separately for each patient.
`
`Again, a death from cancer propelled the field forward. In 2001, a 44-year-old woman, Kimberly Lawrence Netter, succumbed to breast
`cancer. Her father-in-law, Edward Netter, a wealthy financial services entrepreneur, and his wife, Barbara, formed the nonprofit Alliance
`for Cancer Gene Therapy, which issued some of its first grants to Dr. June and Dr. Sadelain. Dr. June also got support from the Leukemia
`and Lymphoma Society.
`
`“Without that,” Dr. June said of the charities, “we would not have had a clinical trial.”
`
`Successes Draw Attention
`
`As the first decade of this century neared its end, the three pioneers were ready for the big moment — testing their treatments in patients.
`They scrambled to be the first to announce peer-reviewed results.
`
`Dr. Rosenberg and colleagues published first, in the journal Blood in 2010. They described a single patient with lymphoma whose tumors
`shrank after treatment. (The patient later received more therapy, and has been free of cancer since.)
`
`But the approach really attracted attention the next year when Dr. June reported that two of three patients with chronic lymphocytic
`leukemia went into complete remission.
`
`One of them, Doug Olson, a chemist from Tinicum Township, Pa., left the hospital and immediately bought a sailboat. He also took to
`running half-marathons.
`
`“It was like this weight that had been sitting there was gone,” said Mr. Olson, who is free of cancer nearly six years later.
`
`Bill Ludwig, a retired captain in the New Jersey Department of Corrections, had already paid for his funeral when he started treatment in
`August 2010. Once his genetically engineered T-cells were unleashed in his system, Mr. Ludwig’s lungs started to fail, his legs ballooned to
`twice their size, his blood pressure dropped and he began hallucinating.
`
`When he emerged from the ordeal, doctors searched for cancer. Detecting none, they ordered another test, certain of error. But there was
`no mistake. Five pounds of tumor had been destroyed.
`
`Mr. Ludwig, now 71, and his wife bought an R.V. “We’re trying to make up for lost time,” he said. He has celebrated the high school
`graduations of five grandchildren and welcomed his first great-grandchild.
`
`As for Dr. June, Mr. Ludwig said: “It’s hard to describe someone who basically saved your life. He lost the one he loved, and turned around
`and saved me years later.”
`
`Money and Rivalries
`
`The 2011 publication of Dr. June’s results transformed the field.
`
`Novartis, the big Swiss pharmaceutical company, licensed the rights to the therapies created in Dr. June’s lab at the University of
`Pennsylvania, throwing aside concerns that treatments manufactured for individual patients would not be good business. That set off a
`commercial rush, flooding the field with cash after years of doubt.
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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
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`While various companies are in pursuit, three are in the lead. They hope to win approval from the Food and Drug Administration to bring
`the first CAR treatments to market as early as 2017 or 2018, although it is not yet clear how easy it will be to get regulatory approval for
`such a novel therapy.
`
`The companies are teamed with academic pioneers: Novartis with Penn; Kite Pharma with the National Cancer Institute; and Juno
`Therapeutics with Sloan Kettering, the Fred Hutchinson Cancer Research Center in Seattle and Seattle Children’s Hospital.
`
`Somewhat predictably, success provoked jostling and envy. Rather than being allies against a disbelieving world, the pioneers now had
`something worth fighting over — credit, and the gleam of a possible Nobel Prize.
`
`While the Sloan Kettering researchers had done some of the early genetic engineering, they did not publish strong results in five patients
`until 2013. By then, they had been scooped by Dr. Rosenberg with one patient and Dr. June with three.
`
`The spotlight further shifted to Dr. June because of his success with Emily Whitehead, a little girl whose miraculous recovery in 2012 made
`her the poster child for cell therapy. When Mr. Parker, the internet entrepreneur, announced in April that he would spend $250 million to
`start a new cancer immunotherapy institute, Emily, now 11, appeared on stage at the launch extravaganza with Lady Gaga.
`
`Dr. June’s 2011 publications did not cite Dr. Rosenberg’s paper from the previous year, prompting Dr. Rosenberg to write a letter to The
`New England Journal of Medicine. Dr. June’s publications also did not acknowledge that the genetic construct he had used was the one he
`had obtained from Dr. Campana of St. Jude.
`
`St. Jude sued the University of Pennsylvania. Novartis sided with Penn, and Juno Therapeutics with St. Jude.
`
`The suit was settled last year, with Novartis agreeing to pay $12.25 million plus possible future payments and royalties. Within days, Dr.
`June sent a correction and letter of regret to The New England Journal of Medicine, acknowledging that the CAR used in his
`groundbreaking 2011 study, and in treating Emily Whitehead, was “designed, developed and provided” by St. Jude.
`Reasons for Caution
`
`Patrick M. Coughlin, who teaches anatomy at the Commonwealth Medical College in Scranton, Pa., now explains the immune system to
`his classes by telling how one man overcame cancer. Only gradually does it become clear that he is referring to himself.
`
`Now 63, Mr. Coughlin noticed a mass the size of a softball in his abdomen in summer 2013. It was a form of non-Hodgkin’s lymphoma.
`Three different types of chemotherapy and a bone-marrow transplant all failed to help him. Desperate, he came to the National Institutes
`of Health campus here last year for the cell therapy developed by Dr. Rosenberg’s team.
`
`The battle between Mr. Coughlin’s genetically engineered immune cells and the cancer was brutal. For four days he had a fever as high as
`105, chills and bed-soaking sweats. Even his brain malfunctioned — at one point he could not count to 10 or write his wife’s name.
`
`But when the battle ended, the cancer was no longer there. “If I had gotten this thing five years ago,” he said of his disease, “I’d be dead.”
`
`Yet for all the excitement, there are reasons for caution. The CAR therapy works now only for patients with some B-cell lymphomas and
`leukemias, which account for only about 80,000 of the 1.7 million cases of cancer diagnosed in the United States each year. It has not been
`successfully used to treat malignancies of the lungs, breast, prostate, colon or other organs.
`
`“The solid tumors that kill over 90 percent of people do not respond to anything we have now,” Dr. Rosenberg said.
`
`Because it is personalized, cell therapy is likely to be frightfully expensive — probably hundreds of thousands of dollars per patient,
`though the companies bringing these treatments to market have not yet said how much they would charge.
`
`Producing the re-engineered cells is lengthy and complex. Some patients have died during the two to four weeks it took to genetically
`modify and multiply their cells.
`
`And the therapy itself can be arduous. First, patients get chemotherapy to wipe out many of their existing T-cells to make room for the
`engineered ones. Once those enter the body, they can set off a ferocious immune response as well as temporary neurological problems like
`memory loss, seizures and hallucinations.
`
`Recently Juno Therapeutics had to temporarily halt its clinical trial after three patients died from brain swelling. The problem arose when
`the company added a second chemotherapy drug to the regimen preparing the patients for the cell infusion. The authorities allowed the
`trial to resume without that chemotherapy drug.
`
`Still, some patients find themselves hoping they get violently ill, since that is a sign the treatment is working.
`
`“Every morning my wife would ask me how I’m feeling,” said Myles Stiefvater, a copier salesman from Newark, Del., who had the
`treatment in 2014. When he said he felt O.K., they were disappointed.
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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
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`Researchers are also finding, to their dismay, that remissions do not always last. The therapy has had its biggest success in acute
`lymphoblastic leukemia, producing complete remissions for 60 percent to more than 90 percent of patients. Yet up to half of those patients
`eventually suffer a relapse.
`
`In some cases, the tumor evolves so that it no longer displays on its surface what the claw binds to, making it invisible to the engineered
`cells. In other cases, the engineered cells might not last long enough in the body, giving the cancer a chance to resurge.
`
`Karen Shollenberger, a student at Drexel University with acute lymphoblastic leukemia, thought she was in the clear after being in
`remission for nine months after a CAR-T treatment.
`
`But in September, as the school year was beginning, the cancer returned.
`
`“My high hopes for the rest of the term were crushed,” Ms. Shollenberger wrote on her blog in October.
`
`She entered a new trial testing a new CAR therapy directed at another protein on B-cells. Again the cancer went into remission, and she
`returned to school.
`
`But fear lurked in her: What if the new therapy also stopped working? That indeed happened recently. Her best hope now is a bone-
`marrow transplant.
`
`“Each relapse is increasingly terrifying as the options continue to shrink,” said Ms. Shollenberger, 22. But, she said, the cell therapies have
`given her nearly two good years.
`
`The big thrust now is to expand the use of cell therapy to additional types of cancer.
`
`The key is to find protein targets that the engineered T-cells can latch on to to kill cancer cells. Ideally, such a protein should be on all the
`tumor cells, so the entire cancer would be eradicated. But it should not be on healthy cells, or they would also be destroyed, causing side
`effects.
`
`“T-cells are very powerful,” said Dr. Campana, formerly of St. Jude and now at the National University of Singapore. “In the same way
`they can eliminate cancer, they can also kill you.”
`
`A protein called HER2, for instance, is found on many breast and other tumors, making it a seemingly good target. But it is also found in
`tiny amounts in the lungs. When Dr. Rosenberg’s team infused killer T-cells aimed at HER2 into a patient, she went into respiratory
`distress within 15 minutes and died five days later.
`
`The treatments work for the blood cancers because there is a good target. But finding these for the most common cancers has been
`difficult.
`
`One problem is that CARs, because of how they are made, can bind only to proteins on the surface of cancer cells. But most proteins made
`by these cells, or by any cell for that matter, are inside the cell, out of reach.
`
`There is an alternative approach that is gaining interest. Patients’ immune cells can be engineered to make what are called T-cell
`receptors, or TCRs. These can recognize proteins inside the cancer cells.
`
`Some experts say TCRs, which have a far wider array of potential targets, represent the best hope of using cell therapy to treat solid
`tumors. There have been hints of effectiveness already in treating one of those, a type of sarcoma.
`
`It might turn out that the best target for each patient will be unique to that person. Scientists are now experimenting with using DNA
`sequencing and other techniques to find the best mutated protein in each person’s tumor at which to aim the claw.
`
`“Think of how dauntingly personalized this is,” Dr. Rosenberg said. “We are using their own cells to treat a unique mutation in their own
`tumor.”
`
`He said this approach might allow cell therapy to be used for most patients.
`
`Many other improvements are on the runway.
`
`Dr. Sadelain and Juno are working on “armored CARs” that not only bind to the target but produce immune-stimulating chemicals.
`Cellectis, a French company, has treated two babies with an off-the-shelf CAR treatment that does not require each patient’s cells to be
`processed. Bellicum Pharmaceuticals is working on genetic switches that dim or shut off the CAR if the treatment is endangering the
`patient.
`
`“We’re in the Model T version of the CAR now,” said Dr. Levine, now the director of the cell production facility at the University of
`Pennsylvania. “What’s coming along are Google CARs and Tesla CARs.”
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`Setting the Body’s ‘Serial Killers’ Loose on Cancer - The New York Times
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`Dr. Rosenberg, who turns 76 on Tuesday, still works nearly every day. “I want to end this holocaust,” he said of cancer. Jesse Dittmar for The New York Times
`
`Still in Pursuit
`
`In February, the Novartis-Penn Center for Advanced Cellular Therapeutics opened on the ninth floor of a Penn medical building, paid for
`mainly by $20 million from Novartis. It has gleaming new laboratory space, clean rooms with the capacity to manufacture therapy for 400
`patients a year, and a great view of downtown Philadelphia. On the wall are photographs of patients with success stories, like Doug Olson
`running a half-marathon and, of course, Emily Whitehead.
`
`Dr. June, who remarried and had two more children, now jets off regularly to attend conferences and give talks. A world map hanging
`outside his office is titled “Where in the World Is Carl June?” It has pins stuck in every location he has been, and a picture of him on a
`bicycle pinned to his location at the moment.
`
`In the last two years he has visited more than 150 cities in more than 20 countries. This year alone he has accumulated more than 200,000
`airline miles. Despite that schedule, he runs ultramarathons and participated in July in the Death Ride, a grueling bicycle race in
`California.
`
`Dr. Rosenberg still arrives at the National Cancer Institute nearly seven days a week. The walls outside his office are covered with signed
`photographs of the hundreds of fellows who have trained under him, many of them now leaders in immunotherapy. Every five years, they
`gather for a reunion, to reminisce and honor their mentor.
`
`Arie Belldegrun, who was a fellow in the 1980s, now runs Kite, the company commercializing the National Cancer Institute’s CAR
`technology. He recounted what happened when he tried to get Dr. Rosenberg to join the company.
`
`“He sits quietly, quietly, quietly, and then he asks, ‘Arie, why don’t you ask me what I want to do?’
`
`“He said: ‘Every day that I go to work, I’m as excited as a kid coming to a new place for the first time. If you ask me what I want to do, I
`want to die on this desk one day.’”
`
`But not before he conquers cancer.
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`“I want to end this holocaust,” Dr. Rosenberg said in the interview. “I think I’m finally getting the hang of what it will take to widely apply
`this to cancers.”
`
`https://www.nytimes.com/2016/08/02/health/cancer-cell-therapy-immune-system.html
`
`9/9
`
`UPenn Ex. 2023
`Miltenyi v. UPenn
`IPR2022-00853
`
`