Forget the lone-wolf scientist, it takes a team

Disis has always wanted to be part of a translational research team, working to transform or “translate” basic-science discoveries made in a laboratory into useful treatments and interventions for patients. This process of taking an idea from the lab to the patient is often called “from bench-to-bedside,” and it requires wide-ranging expertise. The idea of running such a team didn’t appeal to Disis but being a part of one did.

“I wanted to work with specialized personnel who knew how to do things that I had absolutely no idea how to do. And there was nothing like that around. Absolutely nothing,” says Disis, who speculates it might have to do with how we celebrate the idea of the lone-wolf scientist.

However, Disis realized she could attract more brilliant minds by seeking partners united around a goal rather than a person, so she founded the Cancer Vaccine Institute (CVI) — to manage, treat and prevent cancer with vaccines.

Over the course of 20 years, the CVI has become the largest academic group in the U.S. dedicated to the development of cancer vaccines with 15 patents, 30 clinical trials, five vaccines in the marketplace and over 400 patients vaccinated. “I recently learned that we’re among the top 10 producers of cancer vaccines in the world,” says Disis. “You can’t do that unless you have a team.”

Vaccines vs. cancer

Why are vaccines exciting? Because they work, says Disis.

“My grandmother died of diphtheria during childbirth, as did the baby she gave birth to. If you think about it, three generations ago the major cause of death was infectious disease and people lived to around age 50. That’s not the case anymore. Vaccines are undoubtedly one of the top innovations that have changed our lives,” says Disis.

And unlike chemotherapy drugs, which stay in the body for a limited time, vaccine immunity can last forever, especially with regular booster shots. Moreover, vaccines can target cancer at the level of the individual cell, sparing healthy cells and minimizing side effects.

After Disis determined that “a tissue-destructive” immune response was needed to eradicate cancer, she and her colleagues had to develop a vaccine that would generate this response in people and teach the immune system to distinguish harmful cancer cells from healthy ones — a challenging task since cancer is a master of disguise.

Unlike a virus, which the immune system easily recognizes as an invader, cancer arises from one’s own cells, mutating and proliferating. And it has evolved sophisticated ways of evading the immune system. For this reason, the immune system has trouble distinguishing cancer cells from healthy ones, frequently failing to mount a big enough response and allowing cancer to spread undetected.

But for a subset of women with breast cancer, Disis was able to blow cancer’s cover with the discovery that a certain protein in some breast cancer could trigger the immune system.

Wildly successful clinical trials

A huge research breakthrough came when Disis identified that a protein called human epidermal growth factor receptor 2 (HER2) was immunogenic. This protein is found in elevated levels in around 30% of women with breast cancer, causing their cancer to grow rapidly.

This discovery allowed Disis and her colleagues to create a vaccine that trains the immune system to find and destroy cancer cells with this protein. Of the 66 women enrolled in a phase I clinical trial, all had advanced stage (stage 3 or 4) HER2 positive breast cancer, and 80% are still alive today, 10 years after vaccination. Comparatively, the median survival rate for stage 4 HER2 positive breast cancer is five years.

Similarly, a phase I ovarian cancer trial has seen remarkable results, with over half of participants with advanced stage ovarian cancer still alive eight years later, compared to an average survival rate of only 18 months.

Many of these former clinical trial participants still write letters to Disis, marveling at how long they’ve survived with stage 4 cancer. And there is a growing cohort who want to be more involved with research. “That’s why I love this work,” says Disis. “Thinking that I did do something for this person. That’s why we’re all in it.”

Philanthropy’s critical role

From the time an idea is generated — especially if it’s a fringe idea — to the time it is turned into a useful therapy or treatment, philanthropy accelerates the process and supports lifesaving research that might not otherwise receive funding.

Private support launches ideas that federal grantors deem too risky. Take Disis’ microbiome project, for example. With philanthropic investment, Disis and her team are creating a probiotic that could help cure cancer.

The idea came to them after discovering that certain bacteria in our microbiome stimulate T cells that dampen the immune response, and these T cells travel from the gut to tumor sites, assisting tumor growth. So CVI researchers created precision probiotics that increase bacteria that assist the immune response and decrease bacteria that dampen it. They’re finding these probiotics can significantly slow tumor growth and improve immune therapy.

“Our microbiome project started with someone who gave us a donation. Now we have over $3 million dollars in federal funding. We’re developing a new therapeutic in probiotics because of the generosity of this one donor. Then other donors began pitching in, which made us move fast,” says Disis.

Without private philanthropy, everything would slow to a snail’s pace, she says. Grant cycles are long. Private gifts and donations help the CVI complete clinical trials faster and more efficiently. And, most critically, private funding covers essential costs, like the cost of manufacturing vaccines, which means donor funding is needed to create the vaccines for every clinical trial.

Thanks to accelerated research supported by private funding, Disis thinks therapeutic cancer vaccines will be widely available in five to 10 years, and new preventative vaccines for solid-tumor cancers will also soon be available at an affordable price. If the past is any indication, her vision is on track.

“In my one career, we’ve gone from my first research project — trying to figure out whether the immune system had anything to do with cancer — to the FDA approving immunotherapy to treat cancer eight years ago. That’s like going from 0 to 100 in one lifetime,” says Disis. “And this research really makes a difference in people’s lives.”

Written by Eleanor Licata