Pancreatic cancer vaccines eliminate disease in preclinical trials

(Press-News.org) CLEVELAND—Pancreatic cancer has a five-year survival rate of just 13%, making it the deadliest cancer, according to the American Cancer Society. It typically causes no symptoms until it has already metastasized. Surgery, radiation and chemotherapy can extend survival, but rarely provide a cure.

Now, researchers at Case Western Reserve University and Cleveland Clinic are developing vaccines targeting pancreatic cancer that could eliminate the disease, leaving a patient cancer-free. So far, the vaccines have achieved dramatic results in studies with preclinical models.

Biomedical engineer Zheng-Rong (ZR) Lu has been elated by the response in preclinical models of pancreatic ductal adenocarcinoma (PDAC), the most common form of the disease.

“Pancreatic cancer is super aggressive,” said Lu, the M. Frank Rudy and Margaret C. Rudy Professor of Biomedical Engineering in the Case School of Engineering. “So it came as a surprise that our approach works so well.”

More than half were completely cancer-free months later, a result he said he hadn’t seen before.

Lu teamed with immunologist Li Lily Wang, an associate professor of molecular medicine at the Case Western Reserve School of Medicine, to develop vaccine nanoparticles containing antigens—markers that identify for the immune system whether something in the body is harmful. The vaccines they’ve developed produce anti-cancer immunity.

“This platform has the potential to transform clinical care for this devastating disease,” said Wang, also a staff member in translational hematology and oncology research at Cleveland Clinic. “I am excited to see that our novel nano-vaccine worked so well in eliciting vigorous responses from tumor-reactive T cells—which are typically low in numbers and unable to control tumor growth.”

For more than two decades, Lu has been working with nanoparticles comprised of fats, called lipids, which are well tolerated and can be used to deliver drugs and vaccines because they are compatible with living tissue.

PDAC tumors are often comprised of cells with various mutations. To produce anti-tumor immunity to these different mutations, the researchers engineered antigens to the most commonly mutated oncogenes, which drive the overgrowth of cells in cancer. These antigens stimulate and train the patients’ immune system to destroy tumor cells, the researchers explained.

Rather than personalizing medicine for individuals, these vaccines would be effective for many PDAC patients, the researchers hope. The anti-cancer nanoparticles would be injected on a three-dose schedule.

The researchers plan to combine the vaccine therapy with an immune checkpoint inhibitor, which boosts the body’s immune response by keeping tumor cells from turning off the immune cells that would otherwise destroy them. Immune checkpoint inhibitors are approved to treat several types of cancers, often in combination with other treatments, boosting their effectiveness.

Lu said the vaccines could potentially be used to prevent PDAC in patients who might be susceptible to developing the disease because they carry certain mutations.

“We’ve shown that our vaccine generated immune memory in preclinical models,” Lu said. “If we could do that in patients, we could prevent PDAC before tumors start forming, so the vaccines could be either therapeutic or preventative.”

The researchers received a $3.27 million, five-year grant from the National Cancer Institute to further explore the therapeutic use of vaccines in preclinical models of PDAC. Lu hopes to collaborate with industry on demonstrations of safety in other models before moving to clinical trials in human patients.

Jordan M. Winter, professor of surgery, and Akram Salah Shalaby, assistant professor of pathology, both at the medical school, are co-investigators. All the researchers are members of the Case Comprehensive Cancer Center.

 

 

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