Will vaccines transform cancer care?

More than 2 million new cases of cancer will be diagnosed in the United States this year, according to a National Cancer Institute estimate, and 618,000 people will die from the disease. 

But imagine if—after a standard course of treatment—patients could be vaccinated to prevent their cancer from ever returning. 

For example, the partnerships allow researchers to obtain genetic and molecular information from patients’ tumors to help develop vaccines for future patients.

“We have the most amazing science and engineering programs in the country,” said Gary Schwartz, MD, director of the Case Comprehensive Cancer Center, whose member institutions are CWRU, University Hospitals and Cleveland Clinic. “With these resources, we can do things no one else can do.”

Going on the attack

Vaccines train the immune system’s T cells—a type of white blood cell that detects and remembers specific pathogens—to recognize and attack cancer cells and create a pool of T cells that can be activated again and again if more cancer cells pop up later.

“Vaccines can potentially confer lifelong immunity, with memory,” said Peter Anderson, MD, PhD, a pediatric oncologist at Cleveland Clinic Children’s, a professor of pediatrics at CWRU's School of Medicine’s Cleveland Clinic Lerner College of Medicine and a cancer center member. 

As a leading expert in treating Ewing sarcoma—a rare but deadly cancer usually found in children—Anderson is also working to develop a vaccine for the disease.

The concept of stimulating a patient’s immune system to wipe out tumors has ancient roots. Records indicate it dates back millennia to ancient Egypt. In the late 19th century, physician William Coley developed the first anti-cancer vaccines containing killed bacteria, which successfully revved up the immune system and made tumors disappear.

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But in the 1930s, chemotherapy and radiation took center stage in treatments while immunotherapy languished in the wings. A discovery in the mid-’90s changed that.

James Allison, PhD, then at the University of California, Berkeley, and Tasuku Honju, MD, PhD, then at Kyoto University in Japan, each discovered proteins that act as “off switches” for mechanisms that cancer cells exploit to avoid destruction by T cells. The work later earned them the 2018 Nobel Prize in Physiology or Medicine.

Their findings led to immune checkpoint inhibitors, widely used in cancer treatment today, that jam the T cells’ off switches.

“Those discoveries set the stage for a lot of what we’re all doing now in the field,” said Timothy Chan, MD, PhD, who is working on a Ewing sarcoma vaccine and co-directs the cancer center’s Immune Oncology Program. He  also is chair of Cleveland Clinic’s Global Center for Immunotherapy and Precision Immuno-Oncology and a professor at the CWRU medical school.

Preventing cancer—and its recurrence

Researchers are developing both personalized and broadly targeted vaccines, some to prevent cancer and others to keep it from returning.

“Vaccines will likely perform best if they are given postoperatively,” said Schwartz, who holds the Peter and Laurie Weinberger Professorship in Cancer Research at the medical school and is also vice dean for oncology. “You have to get a good immune response, and the larger the tumor, the harder it is for the immune system to counter the disease.” 

Many cancer vaccines use the same mRNA technology as COVID-19 vaccines—genetic instructions that tell cells to make proteins delivered inside lipid nanoparticles. The cancer vaccines teach the immune system to recognize tumor proteins as foreign, prompting immune cells to seek out and destroy cancer cells without harming normal ones. In combination with immune checkpoint inhibitors, they are potent weapons. 

Chan said lipid nanoparticles that proved successful in the COVID-19 vaccine were originally developed for cancer trials. Then advances made during the pandemic were applied back to cancer. 

“Whether it’s colon cancer or pancreas or breast cancer, or Ewing sarcoma,” for patients to receive a vaccine to prevent recurrence of cancer after their primary therapy “would be extraordinary.”
—Gary Schwartz, director of the Case Comprehensive Cancer Center

Mustering defenses 

Case School of Engineering researchers have taken another approach as they design a vaccine for pancreatic cancer, considered the deadliest cancer. They’ve created a novel nanoparticle containing antigens that stimulate and train the immune system to destroy tumor cells. The vaccine, developed with researchers at the medical school, has produced striking lab results: anti-cancer immunity.

Zheng-Rong (ZR) Lu, PhD, is elated with the early success. “Pancreatic cancer is super aggressive,” said Lu, the M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering and a member of the cancer center. “So, it came as a surprise that our approach works so well.” He hopes to secure funding to move to a clinical trial next year.

The Ewing sarcoma vaccine takes a different approach, focusing on a fused gene—created when parts of two separate genes improperly combine—that drives tumor growth. A vaccine clinical trial may begin early next year at Cleveland Clinic, which will draw patients with the disease from across the country, Chan said.

If the vaccine is successful, researchers could seek to extend the approach to other cancers driven by fused genes. “If we can do this,” Schwartz said, “we’ll be doing something no one else in the world is able to do.”

CWRU researchers and their partners are also developing two vaccines targeting breast cancer. One is for triple-negative breast cancer—the most aggressive and lethal form of the disease. The vaccine—which targets a normal protein only found in pregnant or lactating women, or women with the disease—is in clinical trials at Cleveland Clinic, led by G. Thomas Budd, MD, a Cleveland Clinic physician, a professor of medicine at  the medical school and a cancer center member. 

The other targets inherited BRCA1 gene mutations, which predispose women to breast and ovarian cancers. It was initiated by the late Charis Eng, MD, PhD, professor and vice chair of genetics and genomic sciences at the medical school and founding director of Cleveland Clinic’s Genomic Medicine Institute. The vaccine could prevent cancer from developing in people at risk—or recurring in others. The laboratory research is in the early stages of development and led in part by Ying Ni, PhD (GRS ’12, molecular medicine), an assistant professor at the medical school and a cancer center member working on treatments for the BRCA1 inherited cancer syndrome at Cleveland Clinic.

Schwartz envisions a day when vaccines will have a place in the standard repertoire of cancer treatment. “Whether it’s colon cancer or pancreas or breast cancer, or Ewing sarcoma,” he said, for patients to receive a vaccine to prevent recurrence of cancer after their primary therapy “would be extraordinary.” 

For more information about trials, visit clinicaltrials.gov.

Illustration by Vartika Sharma