Profile of the Laboratory of Vaccine and Immunotherapy Delivery: It Takes a Lab to Orchestrate a Vaccine
Pictured above: Bhanu Koppolu is a postdoctoral Fellow and the Biomedical Engineering Laboratory for Vaccine and Immunotherapy Delivery in the College of Engineering. | Photo by Matt Reynolds
Minutes after his boss drills him with questions about results from recent experiments, Bhanu Koppolu is back at the bench, pulling on black latex gloves and checking on millions of T cells taken from a small incubator inside a whiter-than-white lab room at the Engineering Research Center in south Fayetteville. (Also called “killer cells,” T cells help the immune system fight viruses and bacteria; they are the body’s first line of defense against disease.)
Between the bench and microscope on one side of the room and a hooded, sterile cabinet on the other, Koppolu moves effortlessly, almost gracefully, like an experienced chef in a well-organized kitchen. Everything is where it belongs, and his body knows what to do. It’s almost as if he doesn’t have to think. There are no missteps or wasted energy. He moves back and forth, opening doors, adjusting the microscope, spraying and rubbing ethanol disinfectant on his hands, filling vials with a syringe, inserting the vials into a centrifuge, making slides from red liquid that contains the cell clusters.
After earning his doctorate in biomedical engineering earlier this year, Koppolu now works as a postdoctoral fellow in the Laboratory of Vaccine and Immunotherapy Delivery. Investigators in this “translational” lab — in addition to Bhanu, three graduate students and about a dozen undergraduates work in the lab — focus on developing cancer immunotherapies that will have a strong and immediate clinical impact. The lab’s multi-disciplinary approach uses aspects of engineering, chemistry, physics, biology, immunology and nanotechnology.
Today Koppolu is developing proteins, coating them onto the T cells and testing, trying to see how the cells will behave when they come into contact with the proteins. If they work, if the proteins activate the T cells, Koppolu may use them, along with other biomaterials, to design a molecule or drug that will elicit a desired immune response.
“And this is important,” he says, “because these cells are sensitive to IL-12.”
Ultimately, that’s what he wants to know. How will healthy human tissue respond to Interleukin 12 (IL-12), a cytokine that stimulates the body’s immune system to attack a range of cancerous tumors?
Most of Koppolu’s experiments deal with this powerful substance, which once held great promise as a therapy for cancer until it was shelved in the 1990s because of high toxicities. Then, about 15 years after it was shelved, a young scientist working as a postdoctoral fellow at the Laboratory of Tumor Immunology and Biology at the National Cancer Institute made an important discovery and resurrected IL-12 for cancer treatment.
Koppolu’s boss is David Zaharoff, director of the vaccine and immunotherapy lab. Zaharoff was that young scientist who made the discovery about IL-12 at the National Cancer Institute. While there, he combined IL-12 with chitosan, a polysaccharide derived from the shells of crustaceans. With this co-formulation, he discovered a method of delivering the cytokine directly to a tumor while avoiding systemic toxicity. In 2009, Zaharoff set up shop at the University of Arkansas and quickly demonstrated the power of the chitosan/IL-12 combination when experiments eradicated bladder tumors in mice.
Koppolu says it will take at least a few years before the product is ready to turn over to a pharmaceutical company, which will have to buy licensing rights for intellectual property from the university, if that’s the direction Zaharoff chooses.
“But first,” Zaharoff said, “Bhanu must modify and improve the molecule, so that it has the same capabilities and essentially the same properties as the original discovery but is more proprietary and thus ready for commercialization.”
Meanwhile, Koppolu will plug away at the core tasks that define one’s life in the lab: buying equipment and specimens, setting up and conducting experiments, analyzing data, writing and publishing papers.
Sidebar: David Zaharoff
Since coming to the University of Arkansas in 2009, Zaharoff has received more than $3 million in competitive state and federal grants for research in the Laboratory of Vaccine and Immunotherapy Delivery. In 2014, the National Cancer Institute awarded two grants, $416,897 for his work at continuing to develop a new therapy for bladder cancer — doctoral candidate Sean Smith is working on this project — and $1.5 million to advance the molecule and pharmaceuticals project spearheaded by Koppolu.
There are two other significant projects. To glean a better understanding of how IL-12 works and thus make it as safe as possible, Khue Nguyen, another doctoral student, explores the effect the cytokine has on different strains of mice. And Sruthi Ravindranathan, also a doctoral candidate, is working on a post-surgical vaccine to prevent the recurrence of breast cancer. Zaharoff says the ultimate goal of this project is to develop a personalized treatment, because the vaccine would consist of cancer cells taken from the patient’s excised tumor. These cells would be isolated and inactivated before being reintroduced into the patient along with the delivery of other immune stimulating material.