NCInnovation-Supported Melanoma Immunotherapy
Melanoma steals more than health. It steals the ordinary moments people assumed they would have years to enjoy. When it’s caught early, surgery can erase it. But once it spreads, the cancer becomes something else entirely. Families watch treatments fail in real time, each failure another door closing.
That experience is what drives Dr. Rukiyah Van Dross-Anderson.
For nearly two decades, inside her lab at East Carolina University’s Brody School of Medicine, she has refused to accept the limits of today’s melanoma treatments—especially for the patients who don’t respond to modern immunotherapies. She carries the faces of those patients with her.
“Melanoma mutates so quickly that one drug is rarely enough,” she says. “Patients don’t fail the drug. The cancer just finds a way around it.”
Melanoma behaves like a shape-shifter. With one of the highest mutation rates of any cancer, it can change its biological “appearance” faster than a single therapy can keep up. Many chemotherapies barely touch it. Even today’s cutting-edge immunotherapies– drugs that help the immune system recognize cancer– work for only about half of patients.
The rest see no response at all.
“That’s the gap we’re trying to close,” Dr. Van Dross-Anderson explains. Her molecule is designed to do something the body has struggled with– recognize melanoma as a threat.
The drug works on two fronts. It directly triggers apoptosis– the clean, controlled form of cancer cell death that allows immune cells to clear the tumor. And it activates dendritic cells, which serve as teachers for the immune system. Once activated, these dendritic cells train cytotoxic T-cells to recognize the melanoma as foreign. Suddenly, the immune system can see what it had been blind to.
“We’re essentially giving the immune system a vocabulary it didn’t have before,” she says.
Even more promising: in animal studies, the drug shows very little toxicity. It kills melanoma cells while sparing healthy ones– something researchers dream about but rarely see.
But the biology is only half the story. A molecule is just an idea until a chemist transforms it into something real, repeatable, and scalable. That responsibility belongs to Professor Colin Burns, Department of Chemistry, East Carolina University, who leads the synthesis and formulation strategy behind the drug.
He started by mapping the entire synthesis route: eleven steps from small, commercially available building blocks to a complex therapeutic molecule. It was like constructing a cathedral from the inside out.
To preserve precious materials, Dr. Burns “scouted” each reaction in milligram amounts, testing whether the chemistry behaved as expected. Many reactions failed, some spectacularly. Others worked but posed dangers when scaled– flammable reagents, unstable intermediates, purifications that collapsed at higher volumes. What works in a beaker does not always work in a production vessel.
He learned to redesign early steps with commodity chemicals to avoid supply chain bottlenecks. He engineered a new purification strategy in the second-to-last step so the final drug could reach the purity required for human use. Every choice he made had to anticipate the needs of FDA regulators and the demands of scaling to kilogram quantities.
What makes the molecule extraordinary, Dr. Burns says, is its potency. Derived from a prostamide– a class of compounds the body already uses for powerful physiological functions– PMJ2 works at tiny doses, reducing toxicity without reducing strength. Drugs like latanoprost and iloprost, both prostaglandin analogs, have already proven that molecules in this class can become successful therapeutics.
“PMJ2 has the potency and selectivity you hope for your whole career,” says Dr Burns. “The chemistry is challenging, but the promise is worth it.”
For Ph.D. candidate Maddi Craney, the project became real the first time she looked at melanoma cells under the microscope.
She was brand-new to the lab, learning how to run a cell viability assay. The untreated melanoma cells looked thick and stubborn– classic aggressive cancer. But the cells treated with Dr. Van Dross-Anderson’s drug rounded up, detached, and began to collapse. She could actually see the drug working in real time.
“It hit me that this wasn’t just academic,” she says. “This could matter to people who have almost no treatment options left.”
That moment changed the arc of her career. She now wants to stay in translational research, the space where scientific discovery turns into clinical impact.
“This project showed me what it looks like when science has a purpose,” she says.
The NC Biotech Center, the National Institutes of Health, and I-Corps@ECU contributed about $800,000 total, in initial funding which helped to generate the preclinical data. But NCInnovation’s support marked a turning point for the project. Until that moment, the team had solid early data, a molecule that showed promise, and years of work behind it — but none of the resources required to make the leap toward FDA evaluation. With the new funding, they were finally able to take on the essential preclinical work that determines whether a therapeutic can move forward at all.
The grant allowed them to begin scaling up the compound’s synthesis for the first time, shifting from milligram and gram quantities to the larger amounts needed for FDA-required studies. It also supported preliminary toxicity testing, early stability studies, and the formulation work necessary to identify how the drug should ultimately be delivered. Just as importantly, NCInnovation funding made it possible to bring in regulatory specialists and the project’s entrepreneur-in-residence (EIR) — people who helped the team build a complete clinical development plan, outline every FDA-mandated test, and estimate the full cost of progressing toward human trials. As Dr. Van Dross-Anderson noted, there were no other funding mechanisms available to support this phase of development.
Dr. Burns adds, “The project [EIR] was instrumental in building out the Gantt chart which mapped the project schedule all the way to the first patient in the clinical trial. With a clear list of all the tasks and their expected durations, we can allocate our time and resources effectively. From a business perspective, this allows us to predict the total cost which is critical information for attracting investors because they can now make informed decisions on the valuation of the invention.”
While this planning work was underway, the scientific data continued to build. In animal models that preserve an intact immune system — one of the few ways to evaluate immunotherapies accurately — the compound killed melanoma tumors and prompted cytotoxic immune cells to infiltrate those tumors. These observations aligned with what the team had seen in earlier experiments: the drug induces apoptosis in melanoma cells and activates immune pathways critical for recognizing and clearing cancer.
With these preclinical pieces now in motion, the project is entering a pivotal stage. The synthesis needs to scale from grams to kilograms, the full toxicology and stability studies must be completed, and formulation work will determine the drug’s final form. None of these steps are easy, but every one of them is required before the team can approach the FDA for a pre-IND meeting and, eventually, an Investigational New Drug application. For the first time, they have the regulatory framework, scientific evidence, and strategic roadmap to get there. And with NCInnovation’s support behind them, the possibility of a first-in-human study is no longer theoretical—it’s something they can realistically work toward.
