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Cancer treatment has long relied on the same set of tools: surgery, chemotherapy, and radiation. Branden Moriarity ’07 is pioneering a genome-engineered immunotherapy that has had astonishing results.

Over the four months since the treatment, the scans had begun to change. What had once been widespread metastatic colorectal cancer — tumors throughout the 32-year-old’s body — had receded, shrinking over time before disappearing entirely. Today, more than three years post-treatment, she remains cancer-free.

For Branden Moriarity ’07, whose lab pioneered the treatment, the significance of that outcome is difficult to overstate. “It is so incredible to say that you participated in literally curing someone of a disease — it’s beyond fulfilling,” he says. 

For decades, cancer treatment has relied on a familiar set of tools: surgery, chemotherapy, and radiation. Increasingly, however, researchers are turning toward a different approach — one that asks whether the body itself already holds the key to fighting the disease. At the forefront of that shift is Moriarity, whose work in genome-engineered immunotherapy is helping to redefine what cancer treatment may look like in the future. 

Moriarity’s path to this moment was anything but conventional. When he first considered attending St. Olaf College, he was uncertain he belonged here at all. 

“My ACT scores and GPA were definitely below average for St. Olaf applicants, but my parents — who were both custodians at the college — pushed me to apply,” he recalls. “The only reason I got in was because of the TRIO program, which put me into a summer biology course that taught you how to be a successful college student, with your enrollment at St. Olaf contingent on your passing.”

At the time, biology was Moriarity’s least favorite subject. That summer at St. Olaf shifted his perspective, opening the door to a field he would eventually pursue at the highest levels. 

As he progressed through coursework in biology and chemistry, his interest and confidence in the field evolved. Moriarity’s first year was one of intense adjustment, marked by long hours of studying and a determination to keep pace with classmates who had come from more academically rigorous backgrounds. Alongside his coursework, he had several campus jobs, including working as a dispatcher in Public Safety and later working in the science library. His efforts were encouraged by faculty members, particularly Professor Emerita of Biology Anne Walter, who supported him in pursuing research opportunities. 

“ I was fortunate enough to garner a Howard Hughes Medical Institute Summer Research Scholar Award, and so I got to go to the Czech Republic for three months during the summer before my senior year,” Moriarity says. “At that time, I had really narrowed my focus to cancer research, and I was thinking about a future in which I went on to an M.D. or Ph.D. program. So once I got back to the states, I was home for three days before I took the MCAT’s, and once that was done I immediately left again to participate in St. Olaf’s Biology in South India semester program. Those experiences really solidified what I wanted to do going forward, and also gave me my first real taste of what true research was.”

After graduating with majors in chemistry and biology and a concentration in biomolecular sciences in 2007, Moriarity continued his education at the University of Minnesota, where he pursued a Ph.D. at a moment when cancer research was undergoing significant transformation. Traditional approaches had long focused on directly targeting cancer cells through chemotherapy, radiation, and surgery. Increasingly, however, researchers were exploring ways to harness the body’s own immune system to fight cancer. 

“I think that immunotherapy is the cure for cancer — we just have to figure out the optimal way to actually leverage it,” Moriarity says. “Our immune system is our best defense against developing cancer, and so it makes logical sense to redeploy something that evolved over billions of years to prevent cancer to fight it once it is in existence.”

This idea has become central to his work at the UMN, particularly through a form of treatment known as tumor-infiltrating lymphocyte—or TIL—therapy. 

TIL therapy is based on the observation that immune cells are often already present within tumors, attempting to attack the cancer, but ultimately failing. The approach involves removing a portion of a patient’s tumor, extracting those immune cells, expanding and potentially enhancing them in the lab, and reinfusing them into the patient in much larger numbers. While this method has proven successful in certain cancer treatments, particularly in the fight against melanoma, it has been far less effective in others, including gastrointestinal cancers. Moriarity saw an opportunity to improve upon the existing approach by integrating genome engineering technologies. Using tools such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), his team developed methods to alter the genetic programming of these immune cells, enhancing their ability to recognize and destroy cancer. 

One of the key discoveries in this work involved a gene known as CISH. In preclinical studies, Moriarity and his colleagues found that disabling this gene made TIL more effective at detecting cancer, even when tumors attempted to evade recognition. It also improved the cells’ ability to kill cancer and recruit additional immune responses. Building on these findings, the team launched a first-in-human clinical trial to test genome-engineered TIL therapy in patients with end stage gastrointestinal cancers. The process was complex and highly personalized: for each patient, TIL were extracted from a tumor, edited with CRISPR to disable the CISH gene, expanded to billions in number, and then reinfused into the same patient. 

“I think that immunotherapy is the cure for cancer — we just have to figure out the optimal way to actually leverage it.” — Branden Moriarity ’07

The results were significant. In many patients, tumors that had previously been progressing rapidly stopped growing. In one case, the outcome went even further. A patient who had been living with metastatic colorectal cancer for 10 years experienced a complete response, with all detectable cancer disappearing following treatment. 

“We watched the CT scans over months, and the tumor and metastatic disease started shrinking and resolving,” Moriarity recounts. “About six months after the therapy, she was completely cancer free, and now she’s going on three and a half years with no sign of cancer whatsoever, and she’ll be able to live a full life.”

While this outcome was achieved in one of 12 treated patients, it represented a milestone. 

“This was the first time in history that someone has used genome engineered TIL as a therapy,” Moriarity says. “The outcomes that we saw were quite extraordinary, and I am very optimistic about the efficacy of this treatment in the future.”

At the same time, the trial highlighted substantial challenges. 

“One of the challenges is that this is a very expensive, personalized therapy — each patient represented over a half a million dollars, just to get their product and treat them,” Moriarity explains. “The other challenge was it took too long to make their therapy. On average, it was about four months from surgery to infusion of their TIL product. We treated 12 patients in the trial, but we actually enrolled 22, and a number of them died while we were making their TIL product.”

Addressing those barriers to treatment access has become a central focus of Moriarity’s current work. His team is working to reduce both the time and cost required to produce these therapies, with the goal of bringing manufacturing down to approximately 30 days and significantly lowering expenses. At the same time, they are exploring additional genetic modifications to improve effectiveness, with the aim of increasing the number of patients who experience complete responses. 

“One out of 12 had a complete response,” Moriarity says. “Now, the question is: how do we make that six out of 12?”

Following the conclusion of the initial trial, industry funding for the project came to an end. Rather than allowing the work to stall, Moriarity and his collaborators established a new model to continue their efforts. The Minnesota TIL Alliance brings together researchers at the University of Minnesota, clinicians at the Mayo Clinic, and a network of philanthropic partners across the state. Through an initiative called Un-TIL It’s Cured, the group is working to fund the next phase of research and a broader clinical trial that will expand treatment to additional cancer types. In less than a year, the effort has raised $1.5 million of its 5 million dollar goal, reflecting both the promise of the research and the strength of local support. 

“None of this works without all these partnerships,” Moriarity says. “Right now we are seeing fewer and fewer National Institute of Health (NIH) grants, so we have turned to something called venture philanthropy, where an individual or organization donates money to your laboratory, you do the research, and hope that it will generate new intellectual property that brings in revenue, with a portion going back to the parties that invested in the research to fund other philanthropic ventures. So not only does your own research advance, but you also help to move other developments forward.”

For Moriarity, the impact of this work is measured not only in scientific progress, but in the lives it touches. In addition to leading a research lab of more than 30 scientists, he spends much of his time mentoring students and early career researchers, helping to prepare the next generation of problem solvers. 

“Training the next generation of scientists, seeing them succeed and go on to do big things themselves, allows me to have a broader impact of positivity in the world,” Moriarty says. “That is one of the most fulfilling elements of my life.”

His experience at St. Olaf, he notes, continues to shape his work in unexpected ways. Beyond its scientific rigor, the college’s liberal arts foundation helped prepare him for the writing, communication, and critical thinking that are central to his career. 

“A huge part of my job is writing — grants, manuscripts — lots of reading and revising,” Moriarity says. “Having a liberal arts education was a boon to that. I think I was better prepared and had more advanced skills in that area than somebody who went to a school and just did science the whole way through. I’m also more well-rounded — I had to take courses in things that I had no interest in whatsoever, and grew in directions I wouldn’t have for it.”

Moriarity’s connection to St. Olaf also extends beyond his own experience. His wife, Erin Hoffman Moriarity ‘06, whom he met during their time at college, was likewise a double major in biology and chemistry. Together, they share not only a common academic foundation but also a life shaped in part by those formative years on the Hill — a connection that now carries forward into their family life with their two children, Victor and Xavier. 

Looking back, Moriarity’s journey from a student uncertain about attending college to researcher leading first-in-human clinical trials reflects both the unpredictability of individual paths and the potential for innovation to emerge from them. His work now continues at the intersection of science, collaboration, and possibility, driven by a goal that remains as compelling as it is simple: to bring effective, accessible treatments to more patients — and, when possible, to turn moments like that first complete response into something less extraordinary, and more common.