A professor with the University of Houston Cullen College of Engineering has won a grant from the Melanoma Research Alliance to help develop one of the most promising therapies for patients with the disease.
Navin Varadarajan, an assistant professor of chemical and biomolecular engineering, received the Stewart Rahr-MRA Young Investigator Award. The grant gives him $225,000 over three years to study a therapy that has helped melanoma patients who aren’t responding to any other treatment.
This treatment is a form of immunotherapy, an emerging field of medicine that involves engineering human immune cells to fight specific diseases. In particular, Varadarajan will study adoptive cell therapy (ACT).
ACT involves tumor-infiltrating lymphocytes (TIL), immune system cells that physically enter and then attack malignant tumors. In ACT, these cells are extracted from a patient and amplified in the lab. The stronger modified cells are then re-infused into the patient to facilitate the fight against his or her specific melanoma.
Early clinical trials using ACT to combat melanoma have been promising. Roughly 50 percent of patients have responded to the treatment, with some even going into complete remission. “Essentially, ACT has become the last hope for survival for patients with melanoma that aren’t responding to other conventional therapies,” said Varadarajan.
Many other patients, however, don’t respond to ACT at all. Understanding this huge gap in outcomes is the central goal of Varadarajan’s research.
The key to this work is a special polymer slide Varadarajan has developed dubbed the nanowell array. Instead of a flat surface, the slide has tens of thousands of individual chambers, each with a volume of about 50-100 pictoliters. At that size, the chambers are ideal for holding individual cells – an incredibly valuable characteristic, said Varadarajan.
“One of the biggest challenges in biological research is studying individual cells. Standard slides are good for examining cell populations but they can’t isolate specific cells. What the nanowell array does is shrink the container so that its dimensions are similar to those of a single cell. That lets us achieve single-cell resolution,” he said.
In the first stage of this project, Varadarajan will study different sets of modified TIL cells that have not been injected into a patient. His goal will be to identify their specific properties involved in fighting tumors.
He will then take blood samples from ACT patients who have received identical sets of cells. Exposing these blood samples to the nanowell array, Varadarajan will then single out the engineered TIL cells among all the other cells. Notably, most of these TIL cells won’t be those that were originally given to patients. Instead, they’ll be the descendants of those first cells – several generations removed, in fact.
After isolating and identifying these cells, Varadarajan will remove them from the array. He will then clone them by the million and study their cancer-fighting properties, paying special attention to how they have and haven’t changed from the original engineered TIL cells. With all that done, he will match up the different cells with patient outcomes, helping to identify which ones have been the most successful in fighting different types of melanomas.
With this knowledge, researchers and physicians developing ACT for melanoma will be able direct their work toward the most promising treatments, hopefully speeding the development of successful new therapies that can even be targeted to individual patients.
"Immunotherapy is at the forefront of cancer treatment and research. In some cases it has actually resulted in complete remission," Varadarajan said. "To help the most people, though, we’ve got to understand exactly what properties of infused cells are most effective at fighting cancer. This research will help us quickly identify those properties so they can be included in the future rounds of research and clinical trials."
Varadarajan’s collaborator/mentor on this project is Laszlo Radvanyi, professor of melanoma medical oncology research at the University of Texas MD Anderson Cancer Center. Additionally, Richard Willson, a professor in the Cullen College’s chemical and biomolecular engineering department, will serve as the departmental mentor.
This is the third cancer research grant Varadarajan has won in recent months. He also received funding from the National Institutes of Health and the Cancer Prevention and Research Institute of Texas to conduct two separate studies on different immunotherapy-based treatments for lymphoma and leukemia.