"The future of cancer care is gene therapy."
John Wrangle, M.D., a lung cancer researcher at MUSC Hollings Cancer Center, is investigating how the concept of gene therapy might be applied to cancer.
"All of human medicine is going toward gene therapy," he said. In fact, he added, "There are gene-modified humans among us right now. It's not sci-fi. And somebody has to adapt these technologies to cancer."
The Department of Defense's Lung Cancer Research Program recently awarded Wrangle a grant to pursue his concept of using a gene therapy approach to treat cancer.
It's an idea that he's been mulling for about a decade now, Wrangle said. Partnering with Hollings researcher Martin Kang, Ph.D., whose focus is on gene therapy for pediatric respiratory diseases, has meant that the two can combine their research backgrounds to pursue this new strategy.
Hollings provided seed funding through its Idea Award grant in 2023. That was followed by a grant from the National Cancer Institute in 2024 and then the DoD grant.
Wrangle said he's focused on grant opportunities that fund high-risk, high-reward research and expect researchers to move their findings from the lab to the clinical setting as quickly as possible.
There are already FDA-approved gene therapies for conditions like sickle cell disease, hemophilia and Duchenne muscular dystrophy.
"In those scenarios, you're basically identifying patients who lack the expression of a gene, and you're using gene therapy to put a little software program in the nucleus of all cells of that individual with that rare disease to express that gene," Wrangle explained. "It's a replacement of functional normality."
"It's a whole different problem when you are thinking about cancer. You're not trying to restore normality. You're trying to instill cell death, which is clearly not something that you want to do to normal tissues throughout the body."John Wrangle, M.D.
"It's a whole different problem when you are thinking about cancer. You're not trying to restore normality. You're trying to instill cell death, which is clearly not something that you want to do to normal tissues throughout the body."
Wrangle's research will investigate how to deliver instructions to the cells to begin producing, in essence, an in-house immunotherapy and also, critically, how to ensure that the instructions are activated only in cancer cells.
"This is a non-trivial problem, to spatially constrain therapies which result in cell death to the cancer cells themselves as opposed to normal cells," he said.
Wrangle's previous research was on a new immunotherapy combination. Immunotherapy harnesses and directs the body's own immune system to fight cancer. It might turn an immune cell's "off" switch back to the "on" position, using special proteins to prompt the immune cells to act or modify immune cells to target the cancer cells specifically. Wrangle's previous research moved into clinical trials, and now he intends to use the same immunotherapy approach within a gene therapy construct.
By delivering these instructions to the cancer cells, they "become the manufacturing facilities of the therapies of their own demise," he said. "Now the cancer is manufacturing cancer therapies on our behalf as opposed to us manufacturing them in a facility and then administering them to the patient in the infusion center."
Wrangle treated lung cancer patients, and his research focuses on lung cancer as a starting point. But the idea itself could apply to any cancer, he said.
