UW Research Team Moves Cancer Immunotherapy Another Step Ahead

Madison, Wisconsin - With immunotherapy called the top cancer advance of 2015, a new study from the University of Wisconsin Carbone Cancer Center (UWCCC) has provided a key step in monitoring if, and how, the body's own cancer-killing components are working during immunotherapy.

The immune system’s ability to fight cancer is not a new concept – in fact, it is the reason many pre-cancerous cells never become malignant, even in the absence of medical intervention. So-called natural killer (NK) cell cancer therapy is the subject of several recent and current clinical trials, with some, but not all, patients' tumors shrinking in response to the treatment. 

"As with any cell therapy for cancer, you inject the natural killer cells and you hope they shrink the tumor at some point after infusion," said Dr. Christian Capitini, assistant professor of pediatrics at UW School of Medicine and Public Health and an oncologist at American Family Children's Hospital. "I thought there could be an opportunity to monitor and improve that part of the process, where we could see what was going on so that if someone was going to fail on these types of trials we could intervene sooner." 

Current methods used to track cells typically involve radioisotopes, which can be problematic because the signal decays before the NK cell therapy has produced a response. They are also radioactive and, therefore, come with a level of toxicity. Capitini and his colleagues combined NK cell immunotherapy with the labeling agent fluorine-19 in an attempt to monitor the cancer-killing cells in an animal model that could be safely translated to humans. 

"Fluorine-19 is non-radioactive and it's already found in many FDA-approved drugs, such as Prozac, so it should be very safe, but it's never been used to label natural killer cells," Capitini said. "We embarked on a mission to see if we could label natural killer cells in this way, if we could then detect them and if we could see if they are in the tumor." 

In this study, Capitini and his team showed that the labeling had no detrimental effects on the ability of those cells to kill cancer cells in the lab. They then injected labeled cells directly into mice harboring human cancers and, using a specialized MRI to detect fluorine-19, were able to detect the labeled cells for several days in those tumors. 

"I think this is a critical first step because it showed proof of concept," Capitini said. "Now it's a question of scale: MRI in small animals is easier because the space that you're looking at is smaller, so will we pick up the signal when we move to humans?" 

Capitini next plans to work with researchers in the School of Veterinary Medicine to test the MRI detection in a canine model. If they are able to detect labeled NK cells in larger animals, then they will apply for a human clinical trial with the FDA. 

"I think this could break out not so much as a therapeutic but more as a diagnostic: image-guided therapy," Capitini said. "We'll work out the MRI protocols and develop ways to quantify the signal, and it could be used for any cell therapy, not just natural killer cells." 

The study was published in the journal OncoImmunology and was funded in part by NIH grants K08 CA174750, P30 CA014520, UL1TR000427 and TL1TR000429. 

UWCCC members Sean Fain, professor of medical physics and Bryan Bednarz, assistant professor of medical physics and human oncology, were co-authors of the study.

University of Wisconsin School of Medicine and Public Health

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UW Research Team Moves Cancer Immunotherapy Another Step Ahead