by Sarah Gray
“And this person you’re treating who has had some response—does she have the same kind of cancer as I do?”
“No, she has squamous cell.”
“So my best chance of treatment is in a trial with four people in which one person may be responding with some tumor shrinkage but still cancerous, and her cancer is a different type than mine?”
“That’s correct. But we do believe it could work for adenocarcinoma patients as well. That is, we don’t have any reason to believe it couldn’t work; we just don’t have any patients with that type in the trial as yet.”
The great well of positivity and fortitude that had gotten Sue this far crumbled in that instant, and she began to cry. Her best chance was something that hadn’t worked for anybody yet. Without any treatment, her surgeon had said, she had probably less than a year to live. She had a dozen tumors, including one the size of a golf ball protruding from just above her belly button that she could feel with her hand if she pressed down on it. (She had been so horrified the first time she felt it, she never touched it again.)
Despite her tears, Sue managed to ask Dr. Hinrichs to explain what the treatment entailed.
Hinrichs’s boss, Dr. Steven Rosenberg, was the chief of surgery at the National Cancer Institute and a pioneer in the field of developing and treating patients with advanced cancers with gene therapy and immunotherapy. As Jerome Groopman wrote in an article called “The T-Cell Army” in the New Yorker in April 2012, Dr. Rosenberg “developed a strategy called adoptive cell transfer in which T cells are taken from a patient’s tumor and given immune stimulants such as interleukin-2 which cause them to replicate. Then they are put back in the body.” T cells, which get their name from the thymus, where these cells originate, “are a potent type of white blood cell that destroy cells infected with microbes that they recognize as foreign.”
When Dr. Hinrichs first joined Dr. Rosenberg’s group, the two men were focused on melanoma, a cancer of the skin, which, if caught early, is highly treatable and which, if not, is highly lethal. One of the processes they worked on was one in which they removed a patient’s tumor and then grew huge numbers of T cells out of that tumor. In some cases, the treatment made the cancers go away and stay away.
In refining the process, the researchers wanted to identify specific tumor protein, or antigen, that the T cells could target. “What we found was that we could treat the tumors, but we also caused a lot of injury to the healthy tissue that also expressed the antigen,” Hinrichs said. (This occurred because antigens can make both a normal melanocyte and a cancerous melanocyte.) “Patients would develop severe rashes and experience transient hearing and vision problems. It made the therapy untenable.”
Hinrichs became interested in HPV-caused cancers because it was possible to target the HPV antigen in the tumor and spare the healthy tissue. Someone who has an HPV cancer, such as Sue’s cervical cancer, no longer has the virus, but the antigens remain, which are what cause the cancer. “Our best chance,” Hinrichs said,” is to target antigens that are only in the tumor.”
That’s what the trial was engineered to do when Sue Scott arrived on Hinrichs’s doorstep. Her cancer was just what he was looking for.
But nothing came easy to Sue Scott. After assessing her condition, the NIH refused to accept Sue into the trial because she was too sick. By this point she had developed blood clots in her lungs, and those had to be treated first. Then it was discovered that she had hydronephrosis—one of her kidneys was swelling with backed-up urine because a tumor was blocking the ureter that connect the kidney to the bladder. It put her at high risk for infection.
It was recommended that Sue join a chemo trial to see if chemo could reduce some of the tumors. Sue refused: she wanted the immunotherapy treatment. Chemo would sap her strength, and she wanted to be 100 percent.
The only option left was to put a stent into the ureter to prop it open, but such stents are prone to infection. If Sue developed a kidney infection when they had already knocked out her immune system—well, it could kill her.
“I don’t care,” Sue said. “I have to do this treatment. I won’t talk to anybody. I won’t kiss anybody. Just put in the stent and trust that I won’t get an infection.”
While the board at NIH reviewed her case during the fall of 2012, she sent them a handwritten letter begging to be included in the trial. She addressed it to “the kind, heart-led, wise, hard-working and (I’m guessing) dashingly good-looking team of doctors in charge of my fate. Signed, from a gal who had an unfortunate string of events that led me to VBC (very bad cancer).” And because the review coincided with a presidential election, Sue filled the envelope with confetti and wrote “Vote ‘Yes’ on question ‘Sue Scott!’”
At her next monthly check-up, her medical oncologist was extremely concerned. “You’ve been without treatment for over six months now,” she said. “You need to be in treatment. You can’t keep waiting for this immunotherapy.”
“I have to do this,” Sue said.
“Can I be honest with you?”
She thought, The answer to that is always no.
The doctor said, “It doesn’t matter what treatment you do at this point. None of these things is likely to work.”
And that’s when Sue Scott finally lost her temper.
“You’ve got a lot of nerve!” she said. “It matters to me. I know the chances of this immunotherapy working for me are slim to none. I know it hasn’t worked for anybody else yet. But if this is the last good thing I can do for the next person who ends up in this horrible place—and that’s what we’re talking about here—then that’s what I want to do.”
Sue looked over at her mother, who had joined her for this appointment as she had so many others. Her mother was so moved by what her daughter had said, she was crying.
“I guess it’s your decision,” the doctor said.
In her annual Christmas letter that year, Sue wrote to her loved ones, “Even if it doesn’t work for me, maybe the doctors will learn how to help the next woman who ends up here. Maybe this is the final gift I can offer the world.”
Finally, at the beginning of February, after the clots in her lungs had resolved, she was accepted into the trial. In the six months since she had first approached Dr. Hinrichs, only three other patients had been accepted, making Sue patient number eight.
The first step was to put in the stent to fix Sue’s kidney problem, and it worked out great: no infection. Then she had surgery to remove the tumor on her liver to isolate the T cells to be subsequently grown in the lab. It would take five weeks to grow a sufficient quantity, and Sue, being Sue, figured that was enough time for an adventure.
Sue and her mom, Sharon, had always wanted to go to Australia, but Sue figured that now they weren’t going to get there. When she said as much to her mom, Sharon said, “Oh, we’re going to Australia.” The doctors at NIH thought a seventeen-hour flight each way was a bad idea for someone with late-stage cancer—not to mention that while they were there, they would be spending their time in the outback, a hundred miles from the nearest hospital.
It hardly needs to be said that Sue and Sharon went to Australia. When they got back, Sue was energized and ready for the most difficult three weeks of her life.
During her first week back, Sue received chemo to knock out her own immune system. She lost her hair and felt sick to her stomach. At the beginning of the second week, a nurse brought in an IV bag filled with what looked like condensed milk.
Sue’s brother, a super-smart math guy, was in the room at the time, and as the nurse hung the bag up on the IV stand and arranged the tubing to begin the infusion, he asked her, “Do you know how many cells are in there?”
“We sure do. There’s actually a calculation on this bag that tells us how many are in there.” The nurse looked at the bag and began to read off a complicated equation. “I think that comes to seven and a half billion cells.”
Sue said, “Wow! Incredible there are so many in that little
bag!”
When the nurse left the room, Sue’s brother said, “I think she might have gotten the equation wrong and it’s more than that.”
“How could it be more?”
A few minutes later, with the infusion complete, a doctor came in to check on Sue.
“I’m Dr. Yang,” he said. “How do you feel?”
“I feel seven and a half billion cells heavier,” Sue joked.
“Seven and a half? Who told you that?” the doctor said.
“One of the nurses.”
“Well, she missed a decimal place. You’re actually seventy-five billion cells heavier.”
Her brother smiled and gave her a look that said, “I told you so!”
Sue was amazed how fast and painless the infusion had been. But then the really hard part started.
The next day, Sue began to receive doses every eight hours of interleukin-2, a protein that encourages the TILs (tumor infiltrating lymphocytes) to grow. By the time she received the fifth dose, she couldn’t eat and she required oxygen full-time. The next few days were even more brutal, but at the end of the twenty-one days, Sue managed to walk out of the hospital and head home. Now, all she had to do was wait.
Two months later, miraculous news arrived: there was no detectable trace of tumors on Sue Scott’s scans, and her lymph nodes had returned to normal.
Doctors have continued to check Sue every six months, but as of 2015, Dr. Hinrichs was able to tell her, “I think you’re in the clear.”
The science that led to Sue’s miraculous recovery—one she never expected for herself—is complicated and changing all the time. “It’s a fast-moving target,” as Dr. Hinrichs puts it. But Sue, now an advocate for NIH, has come up with an amusing way of describing what saved her life:
“I tell people that my immune cells were like these superintelligent little nerds with pocket protectors that knew my cancer was there and it wasn’t supposed to be but they didn’t have the strength to more than say, ‘Excuse me, I don’t think you’re supposed to be here.’ The doctors took out those little nerdy cells and they sent them to kung-fu school, trained them how to find the cancer cells and kill them, and then they put them back in. Those same cells went and found my tumors and were like, ‘You need to get the eff out,’ like bouncers at a bar. Those little nerdy guys came back with a vengeance and went all through my body and found the tumors and kicked them to the curb.”
Sue’s case was written up—sadly, without any reference to nerdy cells and bouncers—in the March 2015 issue of the Journal of Clinical Oncology. The article gives the game away even in its very title: “Complete Regression of Metastatic Cervical Cancer After Treatment with Human Papillomavirus-Targeted Tumor-Infiltrating T Cells.”
There were a total of sixteen patients in the trial in which Sue participated; only she and one other woman saw their tumors go away. Another woman had some shrinkage of her tumors, but it was temporary.
In the other patients, sadly, there was no response.
What researchers learned in studying Sue’s cells versus the cells of the women who did not respond to the treatment was that the patients with the greatest reactivity against HPV antigens were the ones who did the best in the trial. As a result, doctors now know that potential patients who have a similarly high level of reactivity will have the greatest likelihood of responding well to treatment; and those without the reactivity can be spared a difficult protocol that would cause them unnecessary misery.
Sue Scott didn’t offer herself up for the NIH trial expecting to help herself; rather, she thought she might at least help the next woman unlucky enough to find herself in the same terrible shoes. But Sue was fortunate in two ways: The first was that she got sick when she did; if she’d received the same diagnosis even a year earlier, there wouldn’t have been a trial for her to join. The second piece of good fortune was that the trial protocol worked spectacularly well for her.
The long-term benefit for future patients because of what Christian Hinrichs and his team at NIH learned from the trial is boundless. A handful of patients, only two of whom recovered, have, through their contribution, furthered and augmented the arsenal that medical science has to combat what was once a near-certain death sentence.
And for Sue, she gets to advocate for change with a smile on her face and a joke at the ready.
CHAPTER TWELVE
The Quest Isn’t Over Yet—The University of Pennsylvania
March 23, 2015
The news about the retinas was fantastic. And it meant I started to hope that I could make one more trip to meet the scientists who were working with my son’s donation.
As I thought about ways to most effectively connect with Thomas’s retina researchers, I figured I’d try a new tactic. In keeping with the style of the letters that are often written from donor families to transplant recipients, I penned a “Dear Researcher” email. In it, I explained who I was and what had happened, and asked if they could tell me why they had needed the retinas. I also broached the subject of a lab visit one day.
In September 2014, I sent the email to Christina Jenkins—associate director with Old Dominion Eye Foundation—and asked her if she could forward it to the person who had wanted the retinas. She said that ODEF had never done such a thing before, and though she could not guarantee a response, she would give it a try.
It took two days.
On September 25, 2014, I received an email from Dr. Arupa Ganguly, a professor in the Department of Genetics at the Perelman School of Medicine at the University of Pennsylvania. Dr. Ganguly thanked us for the donation and explained that she was studying retinoblastoma, a rare but deadly cancer that affects children under the age of five.
And yes. My family was welcome to visit her lab.
A few days later Dr. Ganguly and I spoke on the phone. I could feel my heart beating hard; I would never get used to connecting with Thomas’s “colleagues.”
“It is an honor to talk to you,” Dr. Ganguly said. Imagine—an honor. This was almost too much. “I can’t imagine how you must feel,” she went on. “Thomas made the ultimate sacrifice.”
Whoa, whoa, whoa, I thought. Sacrifice? We didn’t kill our son just so we could donate his body to a study. The word seemed to imply that she felt guilty, or somehow indebted to me, and it took me by surprise. I didn’t want her to feel that way at all.
“I don’t see it that way,” I said. “If you hadn’t wanted Thomas’s tissue, it would have been buried in the ground where it wouldn’t be helping anyone. Our choice was not between an alive child and a dead child. We would have picked the alive child, of course. So our choice was between burying our dead child and donating his tissue. Donating to your study added a layer of meaning to his life that was not there before. So we are very grateful he could be part of your study.”
I asked Dr. Ganguly if she remembered receiving the tissue; after all, it was almost five years earlier.
“Yes, I remember that day. I have a log book, but I don’t need to look in it. It’s the only healthy tissue sample we received in six years.”
Dr. Arupa Ganguly had been waiting on a sample like Thomas’s for six years? I was floored. It validated my hunch that donating for research was worth the effort. It did matter to someone—and it mattered a lot. Arupa told me that the tissue was so precious she was saving it, because she didn’t know when she might get more.
And then she said something that stopped my heart.
“I still have some of it in a lab freezer. You can see it if you like.”
Yes, I wanted to see it. Seeing Thomas’s journey from the very beginning to the very end—how many people get to do something like that? To see what a donation looks like, and understand what it means. And to be in the presence of a lost boy’s RNA.
It had been one of the most meaningful phone calls of my life.
Yes, I wanted to see it.
The tour of Dr. Ganguly’s lab was set for Monday, March 23, 2015, which would be the twins’ fifth birthda
y. We decided to make a stop at the National Disease Research Interchange headquarters, too, ahead of our trip to see Dr. Ganguly. In the meantime, Arupa sent Callum a toddler-sized Penn T-shirt for his collection.
Ross, Callum, and I drove to Philadelphia a day early and spent the Sunday at the child-friendly Please Touch Museum. We had a dinner at an Irish pub and carried all of Callum’s birthday presents up to our hotel room so he could open them in the morning. But I couldn’t wait for the next day to arrive.
Callum woke up bright and early that Monday, eager to get on with our celebration of his special day. His favorite gift was a two-foot-tall Godzilla he had been talking about for weeks.
Our appointment at NDRI in Center City was set for 9:30 A.M. When we arrived, an athletically wiry man in his fifties, with a pair of reading glasses perched on his forehead, was waiting in the lobby. I had contacted the Philadelphia Inquirer to see if they thought there was a story in my family’s trip, and they had sent the best of the best: Michael Vitez, a thirty-year veteran staffer with a Pulitzer under his belt for his human-interest stories.
In a conference room, NDRI president and CEO Bill Leinweber and about thirty members of his staff were sitting around a large table.
Bill thanked us for coming: we were, once again, the first donor family to request a visit. I introduced myself, Ross, and Callum to the assembled group.
I gave them my presentation about Thomas and the researchers I had already met, and I thanked them for making this journey possible. When I was done, I handed Bill a framed copy of a photograph of Thomas.
“May I have a high-res digital copy? I’d like to make an enlargement for the lobby here,” he said.
Bill presented Callum with a birthday card and several stuffed animals as presents. I went around the room introducing myself to every member of the staff and thanked them for the work they were doing. It was a privilege to meet the people who were vital to so many groundbreaking medical advancements.