A Vaccine Grown From a Patient's Own Cells for Cancer in the Spinal Fluid

Heather Curley was 32 when a lump she found after a shift at the salon turned out to be stage 4 breast cancer, and 33 when she learned it had reached the fluid around her brain and spinal cord.

Ten months later, she became the second patient to enroll in a phase 1 trial at Moffitt Cancer Center in Tampa, Florida, testing a vaccine made from her own immune cells and delivered directly into her spinal fluid.

On Aug. 10, Curley marked three years since she was diagnosed with leptomeningeal disease, a diagnosis her oncologist had warned her not to Google because of its historically short survival.

What is leptomeningeal disease in breast cancer?

Leptomeningeal disease occurs when cancer cells spread to the meninges, the layers of tissue surrounding the brain and spinal cord, and the cerebrospinal fluid (CSF) that circulates through them.

Curley's diagnosis came by phone on Aug. 10, 2023, the day after a routine brain magnetic resonance imaging (MRI) scan. She was only receiving the scan because another clinical trial covered a cost her insurance would not.

"Of course, I got off the phone with her, and I googled it, and it said this disease is mostly the prognosis is two weeks left untreated, and four months with treatment," Curley said.

Dr. Peter Forsyth, the neuro-oncologist at Moffitt who leads the vaccine trial, described leptomeningeal disease as a serious diagnosis with limited treatment options.

His team has also noticed something they cannot yet explain: Patients who develop leptomeningeal disease from breast cancer tend to be younger than patients with HER2-positive metastatic breast cancer that has not spread to the spinal fluid.

How does the dendritic cell vaccine work?

The experimental treatment uses dendritic cells, immune cells that recognize potential threats and help signal other parts of the immune system to respond.

"We're using the patient's own immune system to turn it against the tumor cells, so which uses dendritic cells, which I call the Paul Revere of the immune system," Forsyth said.

Curley's next step was apheresis, in which blood was drawn through a catheter. The cells needed to make the vaccine were collected and the rest of the blood was returned to her.

The collected cells were then grown for two to three weeks and exposed to HER2 and HER3 peptides, small pieces of proteins associated with cancer cells. The goal was to teach the dendritic cells to recognize those proteins and help direct an immune response against the cancer.

The researchers selected HER2 and HER3 to potentially reach different breast cancer subtypes. HER2 can be highly expressed in HER2-positive breast cancer, while HER3 is found across other breast cancer subtypes, including some triple-negative tumors.

What did treatment involve?

Fifteen patients enrolled in the phase 1 trial. Each received the vaccine through an Ommaya reservoir, a small port surgically placed under the scalp that provides access to the cerebrospinal fluid.

Treatment was given once a week for 12 weeks. Researchers tested increasing doses, from 1 million cells to 50 million cells, to evaluate the safety and tolerability of the treatment and determine a dose for further study.

Curley's path to her first vaccine dose began with 10 rounds of proton radiation to her brain and spine at the University of Maryland in Baltimore. Moffitt did not yet have a proton center.

The radiation left her unable to eat or swallow and using a wheelchair. She then underwent surgery to have the Ommaya reservoir placed, followed by apheresis and the start of weekly treatment.

Her treatment days lasted six to eight hours. The team first removed spinal fluid, administered the vaccine and waited several hours before collecting another sample.

More than halfway through the trial, Curley learned that four additional doses were available. She took all four, extending her treatment to 16 weeks.

"I said I have to do this because I can't have in the back of my mind what if," she said.

After treatment, Curley's MRI showed no detectable disease in her brain or spinal fluid, according to Curley and Forsyth. The first patient treated in the trial, who had a different breast cancer subtype, later died from causes unrelated to leptomeningeal disease. Curley is now the longest-living patient treated on the trial.

What were the side effects of the vaccine?

Headache and feeling unwell were common after treatment. Forsyth said the vaccine intentionally triggered inflammation in the meninges as the immune system responded. This differs from meningitis caused by a bacterial or viral infection.

At the highest dose of 50 million cells, some patients experienced symptoms lasting one to two weeks. Researchers ultimately selected 10 million cells as the dose to move forward.

Curley said vomiting began almost immediately after the vaccine entered her port. She described her headache as a "12 out of 10," accompanied by pain down her spine and between her shoulder blades that could last about 36 hours.

Treatment nights often meant sitting in a dark room in a fetal position before the drive home while her daughter stayed with her grandmother.

The limitation of the phase 1 trial was that it did not formally measure quality of life. Patients facing a disease with few treatment options may minimize symptoms because they want to remain on treatment.

"I've literally caught myself asking, 'Are you okay?' and they would say, 'Yeah, I'm fine.' It's like, no, I don't think you're okay," Forsyth said.

What did researchers find in the spinal fluid?

Researchers also examined how the immune environment inside the spinal fluid changed during treatment.

One of the most noticeable changes involved B cells, immune cells involved in producing antibodies. They accounted for about 1% of cells before treatment and increased to roughly 25% afterward, Forsyth said.

In one patient with HER2-positive breast cancer who is now more than three years from diagnosis, researchers also detected immune activity in the spinal fluid that was not present before treatment. The finding suggested antibodies may have helped immune cells recognize and kill cancer cells.

Forsyth cautioned that the findings do not prove the vaccine caused patients to live longer. The study included only 15 patients, his team is still analyzing the full dataset and several patients did not benefit.

"By no means everybody benefited, but some people really benefited," he said.

What comes next for the dendritic cell vaccine?

A phase 2 trial is now underway.

Patients with HER2-positive breast cancer receive the dendritic cell vaccine followed by Herceptin (trastuzumab) delivered into the spinal fluid. Patients with triple-negative or hormone receptor-positive breast cancer receive the vaccine followed by Opdivo (nivolumab), an immunotherapy designed to help the immune system recognize and attack cancer cells.

Treatment continues for about a year.

Forsyth said Department of Defense funding allowed his team to move from the first study into the phase 2 trial within about two months. Another trial is expected to open in early 2027.

Curley's experience remains one patient's outcome from an early-stage trial rather than evidence that the vaccine works for everyone with leptomeningeal disease. Each year since diagnosis has brought another milestone she once did not expect to reach.

What should patients newly diagnosed with leptomeningeal disease know?

Curley now spends much of her time advocating for other patients while her daughter, who is almost 7, is at school. She has connected several other women with leptomeningeal disease to the trial at Moffitt, stays in touch with patients through online support groups and encourages families to ask their doctors about treatment options and clinical trials.

"So many doctors are not well informed about this, and they are quick to say there's nothing we can do, and they put people on hospice all the time," she said. "Time is not on your side with this disease."

During treatment in Baltimore, Curley wrote 21 birthday cards for her daughter because she did not know how many birthdays she would be there to see. Every year since, she has photographed the cards, still sealed, in the trash can.

"I don't open them, I don't read them, I don't let her see them, but I take a picture of it in the trash can and just relish in another milestone that I've been able to be here for," she explained.

Curley is now the primary caregiver for her daughter and drives her to and from school each day.

"I never thought I would get to see her go into elementary school, and I just was able to be there for her first day of first grade," she said.

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