Taylor returned to NIH for the first time in about a decade on Dec. 12 to be filmed with Rosenberg by producers of an upcoming PBS documentary on the history of cancer. Overseen by Ken Burns, the project is due to air in spring 2015 as a 6-hour series based loosely on Siddhartha Mukherjee’s book The Emperor of All Maladies.
Rosenberg, who came to NIH in 1974 fresh out of a residency in surgery to become chief of the Surgery Branch, saw a toughness in Taylor, a Navy officer, that made him think that much of the tinkering he had done with IL-2 dose and frequency, among other modifications, in previous patients, could be ramped up in her.
“We gave her a very vigorous treatment,” he recalls. “More intensive doses, more frequently. And it resulted in a complete disappearance of her cancer, which has persisted for 28 years.”
Taylor’s remission was a media sensation and was documented in a New England Journal of Medicine paper, on 25 patients, that landed Rosenberg on the cover of Newsweek in 1985. “That paper is one of the most highly cited papers in the oncologic literature,” Rosenberg said.
But media favor, then and now, was not easily won.
Then and now: Taylor looks at a photo of herself and Rosenberg taken in 1984 (and reproduced at right). She said, “I will be forever grateful to not only Dr. Rosenberg but all the hard-working folks at NCI.”
Present-Day Photos: Ernie Branson
Taylor, a native of Wichita Falls, Tex., was a 29-year-old naval officer posted to the Defense Intelligence College when she noticed a suspicious mole on her back.
“I had the doc check it,” she recalls. “You know you’re in trouble when you start seeing a lot of [doctors] fast.”
The mole was surgically removed and Taylor was advised that she had a 50-50 chance of recurrence.
“I made it through school and became flag secretary to an admiral on Guam,” she recalls. “I was there for 3 months when the melanoma came back—three [tumors] on my arm.”
A surgeon biopsied the lumps, confirmed a diagnosis of melanoma and arrangements were quickly made to fly Taylor back to the states.
She had wanted to go to an Air Force hospital in Biloxi, near her family in Pensacola, Fla., but an admiral overrode her decision and sent her to Bethesda’s naval hospital.
“Just by luck, one of the NIH docs was over doing rounds at Navy,” Taylor remembers. She enrolled in an NCI trial being conducted at a small hospital—no longer in operation—at NCI-Frederick. Researchers tried giving interferon and then injecting a monoclonal antibody directly into melanoma lesions.
“My quality of life was out the window,” said Taylor. “I could barely function.” Billeted at a nearby hotel during that trial, she says, “To this day, I’m not keen on staying at Sheratons.”
Within a month it was clear that treatment was failing. “The doctors sat me down for a heart-to-heart and said, basically, ‘We don’t have anything for you.’ They said it was a good time to make what we now call a bucket list.”
Taylor was advised that she had 3 months to live, a figure that was later revised to 17 months when tests revealed no major organ involvement. “I was thrilled to get any additional time I could,” she explained. “It’s just that the doctor said it to me with such enthusiasm, but all I could comprehend was that life as I knew it was over.” Her official Navy personnel file was marked “Death Imminent.”
|Taylor was on campus to be interviewed by PBS for an upcoming series on cancer.
One of the Frederick researchers knew of a new trial being conducted by Rosenberg in Bethesda. But Taylor, with lumps all over her body, had resigned herself to the grim prognosis.
“It took some coaxing from my family” to give Rosenberg’s protocol a try, she recalls. “I didn’t feel that I was giving up. I just felt like I was facing reality.”
Taylor smiles when she remembers first meeting Rosenberg. “He was like Mister Rogers: ‘Come on up to the neighborhood—check it out.’”
Her mission-oriented military toughness began to emerge. “I decided to go into it full-fledge…I’m not one of those people with high expectations. I came with a certain peace of mind. My mom said, ‘Why not try this?’ so I came determined to give it my best shot.”
Taylor was surprised at how big-league NIH was compared to the outpost in Frederick. “It was far more formal and laborious than the little, laid-back Frederick crowd. I had all these tests, and a case manager. I remember them asking me, ‘Do you have any fears or concerns?’ By that point, I thought it was the most ludicrous thing I’d ever heard. ‘No! I don’t have any at all!’
“I finally saw Dr. Rosenberg. He was very soft-spoken, very friendly, going through this list of everything that could go wrong—‘The kitchen sink’s gonna fall on you’—but it didn’t matter to me. He admitted that they had had no success to date.
“What really resonated with me was when he said, ‘I don’t know of any other option you have.’ I thought, well, okay…”
She was in a treatment room in old Bldg. 10 when Rosenberg told her that they were going to dramatically escalate the doses of IL-2. She looked up at a mural on the ceiling, which reminded her of the décor in a scene from the Charlton Heston film Soylent Green. “It looked like this room where they gave people lethal injections. I thought, ‘My God, I think I’ve picked the wrong program!’ But I think I picked the right program after all.”
Rosenberg was so concerned about potential side effects of therapy that Taylor was assigned a 2-person team: a nurse and a clinical fellow. “I was the big rat,” laughs Taylor.
To keep her busy and distracted, they made her choose a crafts project. “I picked a rug to hook,” said Taylor. “That’s so not like me.”
Treatment was, as predicted, tough. “I just sort of took each day at a time,” said Taylor. “I had to regroup. For the apheresis [harvesting of blood cells that would be treated then returned to her body] they had these gigantic needles. I would lay there for 3 hours. You kind of get numb after a while.”
“We gave her more IL-2 than we had given any other patient,” Rosenberg said. “Linda was tough. Not a lot of people could have withstood the treatment.”
Taylor developed fever, chills, the shakes. “I had unbelievable fluid retention. I felt, like, squishy when I walked. Then I wasn’t walking at all. But I don’t remember ever wanting to quit. Obviously, it was incredibly hard for me.”
She remembers becoming enraged at the noises made by a fellow patient’s toy monkey. “Normally I don’t agitate easily,” she said. “I had a tremendous amount of trouble breathing.”
“That was the cytokine storm,” explained Rosenberg; IL-2 therapy induces a massive innate immune response that can cause, as it did in Taylor, pulmonary edema. Researchers have since learned to tamp down the reaction. “We learned from Linda,” he said.
Taylor was intubated for one night for the edema, which soon resolved. In December 1984, she went home to Pensacola in stable condition, but full of apprehension about what was happening inside her body.
A month later she returned to Bethesda. There were no new lumps, but the old ones—which covered her body—had not disappeared. A biopsy of one indicated that the cells inside were dead. “But nothing else changed, there was no shrinkage,” Taylor said.
On her second visit to NIH a month after that, “I could tell that they were smaller,” she said. Adds Rosenberg, “By the third or fourth month, they were all gone.”
Taylor then asked Rosenberg “the monumental question: ‘What does that mean for me?’ He just looked at me and said, ‘I don’t know, we’ll just have to see.’”
Taylor’s eyes fill as she recalls, “I came with peace. But I just thought ‘I don’t know where I am.’ It was always very scary to come back.”
|Rosenberg and Taylor playfully josh one another about who had the higher rank; both topped out as captains in their respective services.
On the off-chance she might live, Taylor started an M.B.A. The Navy, which had put her on temporary disability retirement, was bureaucratically unequipped to deal with a medical miracle; it had no game plan for undoing “Death Imminent.”
It took the intervention of a lawyer, an admiral, a congressman and the Secretary of the Navy to reinstate her to active duty, a labor that somewhat embarrasses Taylor because “I used to handle congressional correspondence in the Navy, and I hated it when people did that.” But regaining her professional identity, and feeling of self-worth, was crucial to her. Being reinstated, she said, “saved my life.”
After being cancer-free for more than 3 years, Taylor went on to become executive officer at Naval Station Pearl Harbor, then XO at Subic Bay (Philippines), then postings in Japan and throughout the Far East. She rose to the rank of captain, which, ironically, placed her in a tie with Rosenberg, who topped out as a captain in the Public Health Service.
Taylor retired in 2001 after 24 years in the Navy. Though she never became a flag officer, she held two command positions: “I wanted command so bad—I wanted it more than anything else. To have two was over the top.
“[But] my mom wanted me to come home—she said, ‘Enough’s enough.’”
During her Navy years, Taylor earned three masters degrees and made two trips to Europe. She now runs a property management company with her brother in Florida.
Rosenberg says the therapy that Taylor withstood over the course of a month at NCI in 1984 now takes only 4-6 days of hospitalization, with significantly fewer side effects. “It’s much easier now…Thousands of people have now been saved by this therapy,” he said. “Linda doesn’t realize how important she is to the history of cancer treatment.”
Though she admits “the fear factor is still real high,” Taylor has had no symptoms over the succeeding years.
“The T cells we modified are still working in your body,” Rosenberg tells her.
“Keep working!” laughs Taylor.
“You won this battle,” says Rosenberg.
Answers Taylor, “It was a tough one.”
Cancer may be the emperor of all maladies, but every once in a while a captain beats an emperor.
To learn more about the upcoming PBS series on cancer, visit www.emperorofallmaladies.org/.
NCI’s Surgery Branch Pioneers Fourth Anti-Cancer Modality
In July 2014, NCI Surgery Branch chief Dr. Steven Rosenberg will celebrate his 40th year in that position. When he began his career, the anti-cancer armamentarium included three weapons—surgery, radiation and chemotherapy. His branch has added a fourth—immunotherapy. Key milestones in that field include:
- 1985 New England Journal of Medicine report on Linda Taylor; IL-2 was the first effective reproducible immunotherapy for the treatment of cancer (approved by the FDA for metastatic renal cancer in 1992 and melanoma in 1998).
- 1988 NEJM article on TIL (tumor-infiltrating lymphocyte) therapy for cancer reported by Rosenberg’s team; it now induces complete durable regression of metastatic melanoma in up to 40 percent of patients.
- 1990 Rosenberg’s team is first to introduce foreign genes into humans.
- 2003 Rosenberg’s team reports, in Proceedings of the National Academy of Sciences, the first use of a checkpoint inhibitor, anti-CTLA4, to mediate cancer regression in patients.
- 2006 Rosenberg’s team publishes in Science the first report using genetically engineered cells to treat any cancer (in this case, melanoma).
- 2010 Rosenberg’s team reports, in the journal Blood, on the first genetic engineering of lymphocytes—adoptive cell transfer—to treat lymphomas using chimeric antigen receptors (CAR).
- 2013 Researchers in Philadelphia report complete remissions of leukemia using CAR therapy pioneered in NCI’s Surgery Branch. Science magazine lauds cancer immunotherapy as “Breakthrough of the Year.”