Cancers in humans have all sorts of ways to survive and thrive: cells and tumors use devious means to deflect, deceive, and evade detection by our body’s immune system.
Take how they fend off cancer vaccines, for example. Cancer cells in the body, whether isolated or consolidated, essentially hide themselves through chemical secretions to remain camouflaged by vaccine agents that would otherwise trigger an all-out attack on the body’s immune system. The fact that the body’s immune system largely cannot “see” cancer is one of the main reasons cancer treatments resort to indiscriminate warfare that kills both healthy and cancerous cells.
Pharmaceutical scientists at the University of Iowa may have discovered a new strategy to defeat cancer’s ingenious defenses. In a new study, researchers found that charged nanoparticles combined with a vaccine were effective in eliminating tumors or extending the lifespan of cancerous mice.
The new approach is attractive, the researchers say, because the nanoparticle could be mass-produced, stored at room temperature and administered by general practitioners to treat various cancers.
“It could be a ready-to-use stable formulation that could be available in powder form,” says Ali Salem, corresponding author of the study and Lyle and Sharon Bighley Chair and Professor of Pharmaceutical Sciences. at UI College of Pharmacy.
The charged nanoparticles – spheres ranging in diameter from 100 to 160 nanometers that were created in Salem’s lab – were injected around melanoma tumors in mice. The nanoparticles act as a sort of beacon, allowing melanoma-fighting cells triggered by the adenovirus vaccine to locate the tumor and overcome its defenses.
In a series of experiments involving nine mice given the nanoparticle-adenovirus vaccine formula, five mice became cancer-free, while the other four survived more than 100 days, more than three times longer than those given only the vaccine and five times longer than those who received the vaccine. Nothing at all.
“It’s a new approach to treating cancer and improving the effectiveness of vaccines,” says Salem. “Historically, vaccines have not had the level of translational success they promised. This approach could finally realize the promise of vaccines to treat cancer.
The adenovirus vaccine jump-starts the body’s cancer-fighting operation by directing a family of immune cells, called cytotoxic T cells, to deploy on missions to find and destroy tumors. But the tumors secrete chemical signals to pass themselves off as non-threatening, and thus largely elude detection. The charged nanoparticles, when injected near a tumor, create an inflammatory reaction, similar to a house fire. T cells circulating nearby see the flames and rush to the site.
“Cationic nanoparticles create localized inflammation at the tumor site,” says Emad Wafa, postdoctoral researcher at the Iowa College of Pharmacy and co-author of the study. “It sends a signal, ‘Hey, come here, we have a situation here that needs to be taken care of.’ Nanoparticles are an essential addition to help the vaccine be effective.”
Other studies have demonstrated success using a combination of an adjuvant — essentially a booster vaccine designed to stimulate a stronger immune response — and a vaccine to locate and erase tumors. In one such study, led by Sean Geary, an assistant scientist at the Salem lab and co-author of this study, researchers injected an adjuvant called CpG directly into mouse tumors, which was combined with an adenoviral vaccine to combat tumors in mice. But CpG didn’t work as efficiently in this study and isn’t as easy to mass-produce.
“We have a synthetic agent that is more cost effective, easier to manufacture, more stable, and would be easier for a doctor to learn and use, compared to a biological agent,” says Salem, who studied vaccines for 23 years. “It’s a conceptually different approach.”
The results were published online on July 20 in Scientists progresspart of the Science family of journals. The study is titled “Cationic Nanoparticles Enhance T-cell Tumor Infiltration and Anti-tumor Immune Responses to a Melanoma Vaccine.”
Co-authors include Rasheid Smith, who received his Ph.D. in pharmaceutical sciences from Iowa and is currently a principal investigator at pharmaceutical company Zoetis; Kareem Ebeid, who earned his doctorate in pharmaceutical sciences from Iowa; and Suhaila O. Alhaj-Suliman, who earned her doctorate in pharmaceutical sciences from Iowa this month.
The National Cancer Institute, a branch of the National Institutes of Health, and Leukemia & The Lymphoma Society funded the research.