Julie Coppage discovered she had ovarian cancer the way many women do—by accident. At age 45 and with one child already grown, the Houstonian had decided to try birth control for the first time. She opted for an IUD, a T-shaped device that releases copper into the uterus as a means of preventing pregnancy. “My sister literally thought I’d lost my mind,” Coppage said of making this decision at an age when women are naturally less likely to get pregnant. “Now she thinks it probably saved my life.”

During a routine checkup after the IUD’s insertion, Coppage’s gynecologist noticed that her ovaries looked abnormal on an ultrasound. Nine tissue samples from her abdomen came back positive for cancer. Soon after, in November 2020, Coppage underwent surgery to remove her reproductive organs—her cervix, fallopian tubes, ovaries, and uterus. During the procedure, the surgeons discovered that the cancer had spread to her omentum as well, so they also removed that fatty tissue that blankets the organs in the abdomen.

Coppage subsequently had six rounds of chemotherapy, taking the drugs carboplatin and Taxol, in 21-day cycles. She responded well to the treatment. In fact, halfway through, scans showed that she was in remission. But some twenty months later, the cancer reappeared, this time in her lymph nodes. Her doctors put her back on chemo—a combination of carboplatin and another drug called Doxil that made her violently ill but didn’t stop the cancer from growing. They eventually determined that her cancer cells had developed resistance to the platinum-based chemotherapy. She would have to seek other treatment options.

Her experience is common among women with ovarian cancer. If caught early enough, the disease is relatively treatable. But it’s rarely caught early, because of a lack of reliable screening mechanisms and because of its generally mild first symptoms—bloating or constipation. By the time most women are diagnosed, ovarian cancer has advanced to stage III, meaning it has spread to tissues outside the pelvis, with a five-year survival rate of 41 percent; or to stage IV, when it has reached the lungs, liver, or other organs and the survival rate shrinks to just 20 percent. In 2022 an estimated 12,810 women died of ovarian cancer nationwide, including 1,055 in Texas.

Initial treatments, which typically involve a combination of platinum-based chemotherapy and surgery, are often successful at eliminating ovarian cancer—at a rate of about 80 percent. But for some 70 percent of women, the cancer eventually returns, and when that happens, it is usually incurable. As effective as the drugs are at first, this form of cancer often develops resistance to them.

Despite enormous advances in oncology, the standard drugs for treating ovarian cancer haven’t changed much in the past thirty years. Meanwhile, immunotherapy, the branch of treatment that harnesses a person’s own immune system to fight disease, has been a game changer in the field ever since Jim Allison, the chair of immunology at MD Anderson Cancer Center in Houston, pioneered the use of “checkpoint inhibitors” in the mid-nineties—work for which he and another immunologist received a Nobel Prize. Allison’s breakthrough has proved highly effective in the treatment of many forms for cancer. Yet it hasn’t benefited a significant number of patients with ovarian cancer.

Initial treatments are often successful at eliminating ovarian cancer. But for some 70 percent of women, it eventually returns, and when that happens, it is usually incurable.

“It’s always been this puzzle,” said Omid Veiseh, a bioengineer at Rice University, who became invested in solving that puzzle after a family friend was diagnosed with late-stage ovarian cancer. She later died. “My mom was very close to this woman, and she kept asking me about what treatment opportunities exist.” His lab, which he started around the same time, in 2017, happened to be across the street from MD Anderson, and he began to walk over regularly to confer with the oncologists there, seeking answers for his family friend. During one of those visits, he met Amir Jazaeri, the director of MD Anderson’s Gynecologic Cancer Immunotherapy Program, who explained the myriad difficulties of treating ovarian cancer.

Over time, these conversations hatched a new mission for Veiseh’s lab, and Coppage may be the first beneficiary of his work. Presented with a menu of possible treatments for her cancer, she enlisted as the first patient in the human trial for his potential solution—what he and his team call “drug factories.”

The Iran-Iraq War was still raging when Veiseh and his family left Tehran, so that his older brother would not be conscripted into military service. They settled in Kirkland, Washington, when Veiseh was eleven, and he grew up envisioning becoming a doctor. But after shadowing physicians during college, he realized that their job was often, well, prescriptive. “Patients came in, they had symptoms, and all [the doctor] could do is follow, like, a rubric of things that they were allowed to do,” he said. “I felt that I wanted to be creative and innovative.”

At around the same time, he learned about the field of nanotechnology, which fired up his imagination with its promise of creating tiny pieces of tech that could be deployed within the body. “I was like, ‘Wow, you can make nanoparticles that can go and access disease sites and repair them,’ ” he said.

Fast-forward to earlier this year, when Veiseh showed me a glass vial containing tiny red beads that sloshed about in a clear solution as he swirled the tube. The dark-haired, baby-faced 43-year-old beamed with an indefatigable energy. The beads resembled a colony of clover mites or the tiny neon-colored roe you might see coating a sushi roll.

Each bead is roughly 1.5 millimeters in diameter and contains some 40,000 cells of the type that you’d normally find on the back of a human eye. These cells have been encased in a porous hydrogel called alginate, the same algae-
derived substance used to make vegan caviar. Veiseh and his lab have genetically engineered the cells to produce interleukin-2, a protein that’s naturally occurring within the body and is a key activator of the immune system’s ability to find and kill cancer cells.

As tumors grow, they develop mechanisms to suppress this immune response. One working hypothesis for why immunotherapy treatments have been less effective against ovarian cancer is that it and the abdominal cavity where it initially spreads—the peritoneal cavity—are particularly immunosuppressive. Proteins such as interleukin-2, part of a category known as cytokines, can combat these effects. “We can amp them up if we can get them to the right place for the right time,” Veiseh said.

Immunotherapy drugs are typically administered by infusion into the bloodstream, using an IV. But that method doesn’t work well against ovarian cancer because the pressure of fluid caused by tumors in the peritoneal cavity can push the drugs back out. Delivering immunotherapy drugs intravenously can also overstimulate the immune system, leading to unpleasant or dangerous side effects, including nausea, vomiting, diarrhea, skin rash, fever, chills, shortness of breath, and even renal failure and fluid in the lungs. “It’s like having the worst flu of your life,” Veiseh said. “It causes a lot of confusion to the immune system because now you have all your immune system activated, and once it becomes activated, it secretes a lot of cell-killing molecules, which can cause a lot of systemic toxicity.”

As Veiseh researched potential solutions, Jazaeri pointed him to a four-year-long study spearheaded in 1995 by a gynecologic oncology researcher at the University of Pittsburgh named Robert P. Edwards, who had the idea to administer immunotherapy drugs near tumors, instead of through an IV. Edwards supplied steady infusions of interleukin‑2 into the peritoneal cavities of ovarian cancer patients by using a pump system that issued the drug through a catheter. In his trial, 6 of 24 patients who had recurrent cancer responded to the treatment, including 4 who were left entirely free of disease. But the process required pumping multiple liters of fluid containing the drug into their abdomens each week for sixteen weeks. This not only was taxing on the patients but also caused serious side effects.

Reflecting on Edwards’s earlier research, Veiseh, with his lab, tried to conceive of ways in which they could eliminate the need for all that fluid. “I was like, ‘Well, this is a problem we can solve as engineers,’ ” he said.
Biologics—drugs derived from natural sources, such as proteins or viruses—are typically made in a bioreactor, a vessel that contains microorganisms and encourages them to thrive. The drugs are then formulated in a lot of liquid to transport them into the patient. Veiseh’s chosen approach was to, in essence, reduce those bioreactors to the size of those tiny beads. “So, you can imagine, two liters shrunk down to this,” he said, holding up his small vial. “This is much easier for the patients.”

The beads could be placed inside a patient’s body, near a tumor, to produce most of the drug at the site, with very little getting into the bloodstream. This would mean doctors could administer much higher doses than typical immunotherapy treatments, without triggering the toxicity that causes debilitating side effects. “The goal is to deliver high local concentrations of interleukin‑2 to rev up the immune system again in order to overcome the immune suppression induced by the tumors,” Veiseh said. “We are trying to shift the pendulum back into the immune system’s favor to help eradicate cancer cells.”

The results of the lab’s preclinical trials were astonishing. Veiseh and his team demonstrated that they could eliminate late-stage ovarian and colorectal cancer in mice in as little as six days. What’s more, the mice seemed to exhibit few to no side effects.

David Miller, chief of the Division of Gynecologic Oncology at UT Southwestern Medical Center, in Dallas, said that given the poor track record of immunotherapy drugs in treating ovarian cancer, he’d be interested in conducting a trial of Veiseh’s “very novel technology”—if the first clinical trial shows promise. “For cancers that involve the peritoneal cavity, like some intestinal cancers and ovarian cancer, that could be significant,” he said, while also careful to note that “not infrequently we cure a lot of mice, and then we come up short on human beings.”

After the success of its animal trials, Veiseh’s team dosed its first human patient, at MD Anderson, in December: Coppage. She had been burned by her experience with Doxil and didn’t want to put her body through toxic side effects again. “I’ve had a lot of people ask me, ‘Why would you do a trial where nobody else has gone before you?’ ” she said. “When you’re given a laundry list of treatment options . . . I’d rather pick something that’s new and exciting and has great potential.”

Jazaeri, who is on the trial team led by gynecologic oncologist Shannon Westin, administered the drug factories into Coppage’s abdomen using a laparoscope, a skinny tube fitted with a camera that helps the surgeon guide it to the right location. Apart from an easily treated fever three days later, Coppage hasn’t experienced any side effects. Her first three scans, taken at thirty-day intervals, showed further growth of the tumor, though it was minimal. Then, in March, her fourth scan showed that the cancerous lymph nodes behind her stomach had shrunk. Doctors hope this means they’ve primed her immune system to continue to beat back the disease.

If the human trials go well, Veiseh and his team hope to test their drug factories with other fast-mutating cancers. By the end of this year or in early 2024, they aim to launch a trial for pleural malignant mesothelioma, a type of cancer commonly tied to exposure to asbestos used in insulation. They also hope to develop trials for colorectal and pancreatic cancers within the next two years. Avenge Bio, the biotechnology company Veiseh created with Jazaeri to commercialize the technology, has secured $50 million in funding. “Cancer is always a game of whack-a-mole, because it’s always changing,” Veiseh said. “I do think this is going to be a big breakthrough. But the proof’s in the pudding, so we have to cure people before we can say that conclusively.”

As for Coppage, she said she has renewed hope. She recently started a rigorous walking regimen, clocking five to six miles a day, sometimes alone, sometimes alongside her fifteen-pound American Eskimo dog named Bella. It’s something she couldn’t have imagined during her earlier treatments. “I feel fantastic,” she said.

This article originally appeared in the May 2023 issue of Texas Monthly with the headline “Tiny Beads of Hope.” Subscribe today.