We could be on the verge of a major cancer treatment breakthrough, with a new vaccine shown to completely obliterate pancreatic cancer cells in preclinical trials. This paves the way for it to move onto the human trial stage.
The pioneering work from Case Western Reserve University researchers targets pancreatic ductal adenocarcinoma (PDAC), the most common cancer that plagues the organ. While pancreatic cancer may not be as prevalent as breast, prostate, lung and colorectal cancers, it's particularly insidious. It commonly remains undetected until it metastasizes, and then treatment is simply to buy more time. The five-year survival rate for this cancer is just 13.3%.
"Pancreatic cancer is super aggressive," said Zheng-Rong (ZR) Lu, a biomedical engineer at the Case School of Engineering. "So it came as a surprise that our approach works so well."
The treatment centers around targeting the most common mutations seen in PDAC tumor cells, using nanoparticles loaded with antigens that trigger the immune system to attack and destroy the cancer growth. In preclinical trials, which generally test novel treatments on isolated cell cultures or animals, the vaccine eliminated the cancer in more than half of the targets.
"Our central hypothesis is that innovative nanosized therapeutic cancer vaccines, specifically targeting multiple mutant oncogenes in pancreatic ductal adenocarcinoma (PDAC), could potentially overcome tumor heterogeneity, thereby achieving a high rate of disease-free survival," the researchers wrote. "Additionally, we believe that the synergistic combination of these nano-vaccines with inhibitors targeting a potent immune checkpoint protein could markedly amplify antitumor immune responses and enhance overall therapeutic efficacy."
Interestingly, the vaccine is an about-face from the trend toward personalized medicine, aiming to be a universal therapy and provide anti-cancer immunity for patients with PDAC and others at risk of developing it.
"This platform has the potential to transform clinical care for this devastating disease," said Li Lily Wang, an associate professor of molecular medicine at Case Western, who also works on 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."
Treatment would involve three injections of the anti-cancer nanoparticles, with a complementary immune checkpoint inhibitor to boost the body's tumor-fighting capabilities, limiting the ability of tumors to evade immune cell detection. And the researchers believe that the treatment could be used as cancer prevention for those who have genetic predispositions to developing PDAC.
"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."
While it's early days, the team has been awarded more than US$3 million in funding from the National Cancer Institute, in order to develop and advance the vaccine. Preclinical trials to further test efficacy and safety in other models are planned, after which the team is expected to undertake human trials.
"To non- invasively assess the therapeutic impact of these nano-vaccines, we will utilize cutting-edge magnetic resonance molecular imaging (MRMI) technology," the team wrote in a project outline. "This approach will not only facilitate the real-time evaluation of the nano-vaccines' effectiveness but also guide the fine-tuning of both the nano-vaccine formulation and the immunotherapy protocol."
The institution is yet to publish new research on the vaccine, but is expected to release data once preclinical trials have concluded.
Source: Case Western Reserve University via EurekAlert!
