Penn’s BRCA cancer vaccine trial aims to prevent the disease in healthy people

Sara Walker was a healthy 39-year-old when she had both her breasts and her fallopian tubes removed to guard against the hereditary cancer that killed her mother and grandmother.

Since then, she has gone roughly every six months for an invasive ultrasound to screen her ovaries, and she will have them removed this year. She follows every recommendation for women like her, who carry a gene mutation associated with a 70% chance of developing breast or ovarian cancer. The mutation prevents the BRCA gene from performing its watchdog role to keep cell growth in check.

Now Walker is volunteering to test a vaccine developed by the University of Pennsylvania and Plymouth Meeting-based Inovio Pharmaceuticals that could spare thousands with the gene mutation from cancer.

Penn researchers believe it is possible to protect people with a BRCA gene mutation from cancer with the prick of a needle, instead of aggressive surgeries and stressful screening regimens that aren’t guaranteed to prevent disease. Walker is one of the first 15 healthy individuals to receive the vaccine as part of a new phase of a clinical trial that began last year.

The vaccine may not dramatically reduce Walker’s risk of cancer, since she’s already had preventive surgeries. Grateful for her current good health, she wanted to help advance science.

Walker, 45, hopes to spare others what she experienced in a whirlwind two years: She learned she was a carrier, had the preventive surgeries, and mourned the death her mother, who had been diagnosed with her third, terminal cancer. Her chest felt tight, thinking of how empty the dinner table would feel without her mother, and how she might miss seeing her own children grow up.

“I felt like our world just collapsed,” said Walker, a child psychologist who lives in Jenkintown.

Most of the emerging cancer “vaccines” are not truly preventive; they are given to people who have cancer and underwent treatment with the goal of preventing the disease from returning. For instance, Moderna’s new melanoma vaccine made waves last year when studies showed it could reduce the risk of death or recurrence among people who had already been diagnosed with the common skin cancer.

Penn’s vaccine is different: It aims to arm the body to recognize the earliest signs of cancer and stop the disease before it develops. The vaccine uses a jolt of electricity to propel DNA deep into the body’s disease-fighting white blood cells. Once inside, the DNA trains them to attack abnormal cells if they begin dividing too rapidly.

Even if the concept works, the vaccine is still seven to 10 years away from becoming widely available to the public, and still must clear many rigorous trials and receive regulatory approval. Penn researchers are cautious, given that dozens of previous attempts to develop cancer-thwarting vaccines have failed.

But the potential is already drawing interest: At least 100 people are on a waitlist for the Penn trial. If successful, the vaccine could change the course of history for families with a deadly genetic code that gives women and men a high chance of developing cancer of the breast, ovaries, prostate, or pancreas. Many have no idea they’re carriers until they’re diagnosed with cancer, sometimes years before routine screening is recommended. And they have a 50% chance of passing on the BRCA gene mutation to their children.

“If there’s a word beyond breakthrough, that’s what it would be,” said Robert H. Vonderheide, director of Penn’s Abramson Cancer Center.

Penn’s vaccine aims to trick the body’s immune system into fighting the earliest stages of cancer at the cellular level, delivered with a jolt of electricity at lightning speed.

Researchers call the approach science’s version of a Trojan horse, the mythological wooden decoy Greek invaders are said to have used to penetrate enemy defenses.

Penn researchers seized on the BRCA gene mutations because they are among the known genetic links to cancer — and therefore clear targets for vaccines, said Susan Domchek, executive director of the Basser Center for BRCA at Penn, who is leading Penn’s trial.

Penn’s vaccine would solve for the out-of-control cell growth that can result from the BRCA mutation by targeting an enzyme called telomerase. Telomerase helps cells multiply as people age from infants to adults. But when telomerase is too active, cells divide rapidly and grow into tumors.

Researchers discovered that they could teach the body’s immune system to recognize and attack the enzyme when it becomes overactive, but before it has time to spur tumor growth.

The vaccine accomplishes this by blasting bits of DNA into white blood cells that are the immune system’s soldiers, leading the charge against infections and diseases.

The DNA, manufactured by Inovio, gives the white blood cells new marching orders: Seek out and attack the enzyme.

For patients, the process involves four shots, each followed by three zaps with a wand-like device that delivers a small electric shock over the injection site. As DNA is electrically charged, this sends the vaccine deeper into the body, through the muscle and into cells.

Trial participants say the experience feels like a hard punch in the arm. It leaves a ring of pinprick punctures around the vaccine injection site.

Penn’s vaccine is one of several in early trials nationally that attempt to prevent cancer.

Vaccines in development at Johns Hopkins University, MD Anderson Cancer Center, and elsewhere use different techniques — such as creating an immune response with deactivated cancer cells, instead of reprogramming white blood cells with DNA.

But they share a common philosophy: The body’s immune system is so powerful that it can protect against cancer, just as it protects against viruses.

“I don’t want to oversell it,” said Elizabeth Jaffee, the deputy director of Hopkins’ Sidney Kimmel Comprehensive Cancer Center. But she feels scientists are closer than ever. “We will get there.”

» READ MORE: UPenn scientists among those developing vaccines that arm the immune system to fight cancer

Families with hereditary breast cancer are eager for better options than preventive surgeries, ongoing testing, and wishing for luck.

“There has to be a less barbaric way,” said Adrienne Fox-Miniman, of Glen Mills. She was 40 when she was diagnosed with breast cancer in 1990. While not part of the clinical trial, she hopes it will help her family.

Fox-Miniman, now 75, has a BRCA gene mutation. So do at least seven other relatives. Her family is Ashkenazi Jewish, which means they have a 1 in 40 chance of carrying the gene mutation, compared to the general population’s 1 in 200 risk.

A niece learned she was a carrier too late; she died of breast cancer at age 34. Fox-Miniman doesn’t speak to the niece’s father, her brother, in part because she can’t forgive him for not getting tested.

Fox-Miniman’s cancer was caught early enough that she decided against a mastectomy to remove her breasts. She opted instead for more screening.

She’s long lost track of how many times doctors have grown concerned enough to inject a long needle into her chest to biopsy a lump. Most times the results are negative, but waiting for the phone to ring remains a near-constant anxiety decades later.

Last fall, doctors found her cancer had returned, and she completed radiation earlier this month.

She tries to keep her mind off cancer by focusing on her grandchildren, who visit often for play dates and sleepovers in a living room plastered with family snapshots.

Her two sons with children do not have the BRCA mutation, so Fox-Miniman doesn’t worry about passing it on to the grandkids. But she tears up reflecting on her family’s painful cancer experience and contemplating a future when a family history of cancer won’t mean a lifetime of forebodings.

“It gives me goosebumps,” she said.

Domchek was surprised by the outpouring of interest in the trial, which requires a significant time commitment. Participants must have lab work done every two weeks between each of the four shots, all of which must be done at Penn’s Basser Center in West Philadelphia. The lab will monitor them for two years after they are fully vaccinated.

“We’re trying to advance science, but we can’t do that unless the first person steps up and holds out their arm,” she said.

Penn began its clinical trial in 2021, with a group of 16 people who had previously been treated for cancer. Researchers began testing the vaccine on the first group of healthy individuals last year. They will all be fully vaccinated by June.

Penn is already enrolling the next group of 12 healthy individuals.

Filko Prugo, a PhD candidate and father of three living in New York City, didn’t think twice about enrolling. He quit his job at an international law firm to study cancer research after his brother, also a carrier, died of breast cancer at age 48.

“I think my first and strongest reaction was just hoping that my kids don’t have it,” Prugo said.

BRCA genetic testing is not recommended for children, but many get tested in their 20s or 30s, when their risk becomes greater.

Sara Walker, the Jenkintown woman who had a preventive mastectomy, thinks her mother would be proud of her for volunteering for Penn’s trial and doing what she can to limit the risks of cancer in their family.

Walker has three children under age 14. She hasn’t talked to them about the possibility that they share a genetic mutation with a high risk of cancer.

She’s hopeful they’ll never have to worry about it.

“I worry about accidents and heartbreak,” she said, “but I don’t think I’m going to worry that my kids will have to go through the same things I did.”