Dr. Catherine Wu, an oncologist at Dana-Farber Cancer Institute, received the Sjöberg Award in honor of her "decisive contributions" to cancer research. (Credit: Courtesy of Dana-Farber Cancer Institute)

(CNN) --

Finding a cure for cancer is a motivating force for many aspiring doctors. There are few who come close to achieving that goal. Among them is Dr. Catherine Wu, an oncologist at the Dana-Farber Cancer Institute in Boston, who has had cancer in her sights since second grade, when a teacher asked her and her classmates what they wanted to be when they went greater.

"That's when there was a lot of coverage about the war on cancer," he said. "I think I drew a picture of a cloud, probably a rainbow, and I drew myself like making a cure for cancer or something."

That childhood doodle was prophetic. Wu's research has laid the scientific foundation for the development of cancer vaccines tailored to the genetic makeup of an individual's tumor. It's a strategy that looks increasingly promising for some difficult-to-treat cancers, such as melanoma and pancreatic cancer, based on results from early-stage trials, and may ultimately be widely applicable to many of the roughly 200 forms of cancer.

The Royal Swedish Academy of Sciences, which selects Nobel laureates in chemistry and physics, last week awarded Wu its Sjöberg Prize in honor of his "decisive contributions" to cancer research.

Cancer treatment has "progressed over the years, but there are still many unmet medical (needs) for many forms of cancer," said Urban Lendahl, a professor of genetics at Sweden's Karolinska Institute and secretary of the committee that awarded the award.


  • Experimental cancer vaccine combined with immunotherapy continues to show benefits against melanoma, trial shows

Dr. Catherine Wu and her close collaborator, Dr. Patrick Ott, have been working on a vaccine to treat melanoma. (Credit: Sam Ogden)

Cancer treatments with mallets

The most common treatments for cancer (radiotherapy and chemotherapy) are like sledgehammers, hitting all the cells and often damaging healthy tissue. Since the 1950s, cancer researchers have been searching for a way to activate the body's immune system, which naturally tries to fight cancer but is overwhelmed by it, to attack tumor cells.

Progress on that front was lackluster until about 2011 with the arrival of a class of drugs called checkpoint inhibitors, which stimulate the antitumor activity of T cells, an important part of the immune system. The work led to the 2018 Nobel Prize in Medicine for Tasuku Honjo and James Allison, the latter winner of the 2017 Sjöberg Prize.

These drugs have helped some people with cancer who would have been given months to live survive for decades, but they don't work for all cancer patients, and researchers continue to look for ways to rev up the body's immune system against cancer.

Wu's fascination with the powers of the immune system arose after witnessing bone marrow transplants as an internal medicine physician and seeing how they rebooted the blood and immune system to fight cancer.

“I had had really formative academic experiences that made me really interested in the power of immunology,” he said. "In front of my eyes were people who were being cured of their leukemia thanks to the mobilization of the immune response."

The 2018 Nobel Prize winners in medicine, Japanese scientist Tasuku Honjo, left, and American scientist James P. Allison, laid the foundation for a new class of anti-cancer drugs. (Credit: Christine Olsson/AFP/Getty Images)

Wu's research focused on small mutations in cancerous tumor cells. These mutations, which occur as the tumor grows, create proteins that are slightly different from those in healthy cells. The altered protein generates what is called a tumor neoantigen that the T cells of the immune system can recognize as foreign and therefore susceptible to attack.

With thousands of potential neoantigen candidates, Wu used "extensive laboratory work" to identify neoantigens found on the cell surface, making them a potential target for a vaccine, Lendahl said.

"For the immune system to have a chance to attack the tumor, this difference must manifest itself on the surface of the tumor cells. Otherwise, it would be quite useless," Lendahl added.

  • Can just one dose of the HPV vaccine protect against cancer? This is what science says

"A fantastic discovery"

The idea of ​​a cancer vaccine has been around for decades. The widely used HPV vaccine attacks the virus that is linked to an increased risk of cancer of the cervix, mouth, anus and penis. However, in many cases, cancer vaccines have not lived up to their promise, largely because the right target has not been found.

"The ability to identify neospecific tumor antigens has become a major field of cancer research, as it offers the possibility of generating tumor-specific cancer vaccines," said Hans-Gustaf Ljunggren, professor of immunology at the Karolinska Institutet. , in a video shared by the Royal Swedish Academy of Sciences. "This is a fantastic discovery."

By sequencing DNA from healthy and cancerous cells, Wu and his team identified tumor neoantigens unique to a cancer patient. Synthetic copies of these unique neoantigens could be used as a personalized vaccine to activate the immune system to attack cancer cells. Wu and her team wanted to test this technology in patients with advanced melanoma in a trial.

The idea that each patient involved in the trial would receive an individualized vaccine was initially difficult for the U.S. Food and Drug Administration, which regulates clinical trials, to grasp, Wu said. Normally, the FDA would require that vaccines be tested in animal experiments first.

Wu and his team made their case: "That courtroom was full. It was the first (trial) of its kind and there were people from many different offices. Our argument was: 'This is custom, anything we do on an animal doesn't really match.' with the human being, so why go down that path?'".

Several cancer vaccine trials are currently underway, but they are small scale. More work is needed before they are viable treatment options for many cancer patients. (Credit: Matt Stone/MediaNews Group/Boston Herald/Getty Images)

Once FDA approval was obtained, the team vaccinated six patients with advanced melanoma with a course of seven patient-specific neoantigen vaccine injections. The groundbreaking results were published in a 2017 paper in Nature. For some patients, this treatment caused immune system cells to activate and target tumor cells. The results, along with another paper published the same year led by the founders of the mRNA vaccine company BioNTech, provided "proof of principle" that a vaccine can target a person's specific tumor, Lendahl said.

A follow-up by Wu's team four years after patients received the vaccines released in 2021 showed that immune responses were effective in keeping cancer cells under control.

"I'm grateful for all the patients who participated in our trial because they are...active partners," Wu said. "It's hard enough to go through treatment, but then go through treatment whose benefit is unknown, and be willing to come in for all the extras we need to do this type of research. There are more tests, more blood draws, more biopsies".

Since then, Wu's team, other medical research groups and pharmaceutical companies, including Merck, Moderna and BioNTech, have further developed this field of research, with trials underway of vaccines that treat pancreatic and lung cancer, as well as like melanoma.

Questions without answer

All ongoing trials are small-scale and typically involve a handful of patients with advanced-stage disease and a high tolerance for safety risks. To prove that these types of cancer vaccines work, much larger randomized controlled trials are needed.

"The numbers are small, I mean, for obvious reasons," Lendahl said. "The data (looks) encouraging, but of course we are still in the early days."

Scientists are also discovering the most effective way to format vaccines. Wu's group and others have used vaccines made from peptides or protein chains. Moderna and BioNtech use mRNA, which the companies pioneered in developing Covid-19 vaccines, to deliver a set of instructions to cells to make the relevant proteins.

"I think there are many paths to Rome. I think there are many different delivery modalities, but each delivery approach can be optimized with different details," Wu said. "There has to be investment and how to make that delivery approach work better. And right now there is a huge appetite for mRNA, you know, fueled by our pandemic."

Cancer vaccines have shown most promise in what oncologists colloquially call "hot tumors" that mutate rapidly, such as melanoma, which was Wu's initial focus. It is unclear whether they will be effective against "cold tumors" such as breast cancer, which are more inert.

"It's easier if more mutations spontaneously occur in the tumor because you have a better smorgasbord of potential small molecules to choose from to make your vaccine," Lendahl said.

Another challenge is how to make these vaccines more cost-effectively and faster so they can reach large numbers of cancer patients, Wu said. Right now, it can take weeks, if not months, to manufacture individualized vaccines at a cost of hundreds of thousands of dollars. One active avenue of research is the development of vaccines targeting neoantigens shared by patients with the same type of cancer, raising hopes for an “off-the-shelf” vaccine that many people could use without a lengthy customization process.

Another question is whether vaccines will work better in combination with other treatments to make them a more effective tool, and if so, which ones.

Trial results, published late last year, found that a vaccine, developed by Merck and Moderna, given to patients with advanced melanoma along with a type of immunotherapy called Keytruda, a checkpoint inhibitor-based drug, led to at a lower risk of recurrence or death than those who received the drug alone, the companies said.

It is also unknown at what point in the treatment cycle vaccines will be most useful: treating cancers detected early, helping patients with advanced disease, or ensuring patients remain cancer-free. Most of the ongoing trials involve patients with late-stage cancer or in remission, but Wu said he believes the vaccines may be more effective in early-stage disease.

Despite the long list of unknowns, for some involved in these initial cancer vaccine trials, the results have been life-changing.

"I'm very grateful that they allowed me to take it," Barbara Brigham, who received a personalized pancreatic cancer vaccine that BioNTech is testing, told CNN last year. She got to see her oldest grandson graduate from college, a moment she didn't think she would live to see. “The opportunity and timing were perfect,” she said. "She helped me and I hope she helps someone else."

-- CNN's Brenda Goodman contributed to this report.