University of Florida: The Turbo Engine That Immunotherapy Needed

Immunotherapy is a hot topic of conversation when it comes to cancer treatment. Pediatric oncologist Dr. Elias Sayour and his team have found a way to make a hot tumor, their way to make immunotherapy, an alternative to chemotherapy, more effective.

“I spend the bulk of my time doing research, 80 percent of my time trying to develop new therapies for childhood cancer,” said Sayour, an associate professor of neurosurgery and pediatrics and principal investigator of the RNA Engineering Laboratory within the University of Florida Brain Tumor Immunotherapy Program. “What we do to take care of children with cancer is largely provide medicines called chemotherapy.

“These are medicines that can work against cancer, but they also can cause a lot of toxicity. And they don’t protect you after they’re out of the bloodstream.”

His team, which includes Hector Mendez-Gomes, Sadeem Qdaisat, Duane Mitchell, and Brandon Wummer – is trying to develop immunotherapy, which holds that your own body should be able to sense foreign cancer cells and tumors in the body to attack them as if they were a virus or other pathogen. A beautiful concept, but with limited efficacy; immunotherapy has demonstrated only a 15-20 percent effective rate.

Inventors Sadeem Qdaisat, Hector Mendez-Gomes, and Elias Sayour pose with UF Research Vice President, Dr. David Norton, on stage at Standing InnOvation.
“Cancer has evolved to prevent immune recognition,” explained Sayour. His team recently received the 2021 Invention of the Year award from UF Innovate | Tech Licensing for their intratumoral Type 1 interferons that sensitize response to checkpoint inhibitors.

Making immune checkpoint inhibitors more effective
The body has natural immune checkpoints that regulate the immune system in an attack against pathogens so the body doesn’t attack healthy host cells. However, these immune checkpoints can also protect cancers from the body’s natural immune defense.

Sayour began his journey by asking the question “Why are some cancers really good at turning off the immune system?”

Immune Checkpoint Inhibitors are a subset of immunotherapy. They are drugs that work by blocking the body’s natural immune checkpoints and are approved for a variety of cancer types, including skin and lung cancer. Sayour and his team sought to improve on this form of therapy.

When cancers successfully escape immune recognition, they sever the communication line to the immune system. Sayour and his team theorized that if they could determine which communication line was severed, they might be able to reverse the process.

His team’s investigation showed signaling molecules, interferons, to be one of the key links in activating the immune system. In combination with immune checkpoint inhibitors, the early release of interferons helps to activate the immune system more effectively.

Turning Cold Tumors into Hot Tumors
“He can turn what you can call a cold tumor into a hot tumor,” said licensing officer Hera Lichtenbeld, who manages Sayour’s technologies. “And that means when you use immunotherapy, which nowadays is still very promising but not always successful, you turn it into a responsive tumor for this immunotherapy.”

A protein on the surface of B and T cells, known as Programmed Cell Death 1 (PD-1), is responsible for attenuating the immune system and suppressing the activity of T cells. This is normally a good mechanism to prevent T cells from attacking healthy tissue, otherwise resulting in autoimmune disorders. However, when cancer cells overproduce PD-1 targets, they escape detection of the immune system. This is what they would call a cold tumor.

The PD-1 pathway becomes an overactive immune checkpoint in these cancers that escape the immune system. Immune checkpoint inhibitors attempt to reverse this phenomenon to activate the immune system, but often tumors are resistant. Sayour and his team found that the early secretion of interferons promotes responsiveness to immune checkpoint inhibitors.

Interferons are the signaling molecules that cue the immune system to attack. To rescue interferon response in tumors, Sayour has leveraged mRNA technology as a method for delivering these cues. This activation by interferon release creates the hot tumor, a tumor on the immune system’s radar.

Helping one child at a time
“The beauty of the immune system is that if you educate it against a child’s cancer, it can remember that cancer and remember it for life so that it’s providing continual protection,” said Sayour. He wants to develop immunotherapies effective enough to be an alternative to chemotherapy.

Lichtenbeld, who nominated Sayour’s technology for the award, describes available cancer treatments as outdated.

“We are still using technology from the ‘60s,” she says. “We know it can be better, and we want to make it better.”

Sayour’s technology has the potential to change cancer therapy, Lichtenbeld said, and working with the UF Innovate office is the best way to make that happen. When inventors work with UF’s Tech Licensing office, they protect their intellectual property and make it more attractive to potential licensees.

“Publishing and providing the world with Sayour’s discoveries may seem like the noble thing to do,” she said, “but it actually hinders growth and development of the technology. It may prevent it from being implemented in clinical use.

“Many companies may be attracted to the technology, but then the question becomes, ‘Are my competitors five steps ahead of me already?’ It discourages companies from exploring R&D of the technology. Through licensing, companies have the security of knowing they have exclusive access to the use of the technology.”

Lichtenbeld believes licensing gives the technology the best shot at making a difference in cancer treatments at the clinical level.

“Without licensing, it’s ultimately impossible to make the work truly matter,” Sayour said.