Big Ideas

Duane Mitchell, M.D., Ph.D.

Imagine reading a book in college that inspired you enough to determine your entire career path. That’s exactly what happened to Duane Mitchell, M.D., Ph.D., of the University of Florida College of Medicine. Although he knew as early as 6th grade that he wanted to practice medicine, it was reading The Transformed Cell by Steven A. Rosenberg, M.D., Ph.D., while at Rutgers College that led Mitchell to the cancer research field.

“Rosenberg’s story of how he was applying research he was conducting in the laboratory to developing new immunotherapy approaches for cancer was captivating,” said Mitchell. “I was pretty much hooked.”

Mitchell, who received a 2017 Translational Grant from the V Foundation, is developing new immunotherapy treatments for children with brain tumors who have developed resistance to standard therapy. The approach, called adoptive cellular therapy, involves collecting immune cells from a patient with cancer, activating them against their own cancer, expanding to larger numbers and then delivering those cells back to the patient.

“By gathering genetic information from the patient’s brain tumor and the genetic background of the patient’s immune system, we can identify what changes in the tumor cells their immune system will likely recognize,” said Mitchell.

He and his team then use “HiPerGator,” the university’s supercomputer, to determine a roadmap for particular targets in that patient, and they can then develop a personalized immunotherapy treatment. Initial results of this study have been promising, and Mitchell is optimistic about the road ahead.

“The most exciting thing to me is that we have tested ‘first-generation’ approaches of this treatment in patients already and have seen remarkable responses in some cases,” said Mitchell. “The research we are doing now will hopefully significantly increase the potency and effectiveness of this treatment. I think the whole field of immunotherapy is energized by the knowledge that resistant and aggressive cancers can be successfully treated using the immune system.”

An important hurdle for Mitchell and other researchers moving forward will be to learn why some patients respond to the new treatments and others do not. Every patient’s tumor is unique, and there are many different types of tumor cells even within a single patient’s tumor. If researchers are able to identify which genetic alterations inside a tumor cell are good targets, they will be able to develop a very individualized approach to attack the tumor. That allows for better monitoring of the patient’s response to the treatment and provides less risk of unintended immune responses against normal cells.

While there are more hurdles to clear, the progress is obvious to Mitchell.

“In my time since starting medical school, I’ve witnessed ‘incurable’ and almost universally fatal infections become manageable with effective treatments and observed complete clinical responses to immunotherapy treatments in cancers previously classified as untreatable,” he said.

While many cancer patients still do not respond positively to immunotherapy treatment, Mitchell said he feels there is a real sense of urgency in the field that is leading to more and more benefits for patients.

“In many ways, being in the field today is like watching a dream unfold in real time,” said Mitchell. “It would be my hope that we will one day view all cancers, including brain tumors, as serious but treatable and curable conditions. I am very optimistic that my children will grow up with a very different perspective of what it means to be diagnosed and treated for cancer than I did.”