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Get the most interesting and important stories from the University of Pittsburgh.Cancer, according to Pitt Department of Medicine Assistant Professor Jason Lohmueller, is a “tricky beast.” It changes in response to therapies and, as far as treatment is concerned, it’s sometimes better to think about it as multiple diseases at once.
With a new modular technology to deliver immunotherapies to cancer cells, Lohmueller he believes he has helped create a weapon to slay that beast. And together with collaborator Alex Deiters, a chemistry professor in Pitt’s Kenneth P. Dietrich School of Arts and Sciences, he co-founded the startup Monarch Therapeutics to translate this innovation from the lab to the market.
“We want to take a multi-targeted approach to keep cancer from escaping,” Lohmueller said. “This adaptable technology that Monarch is developing, I think, will be the key to getting there.”
A Swiss army knife
Some scientific collaborations start because of a paper or a conference presentation — the one between Lohmueller and Deiters began with a couple of undergraduates. A team of students looking for faculty advisors to compete in the iGEM synthetic biology competition sought out both Lohmueller and Deiters, who, after jointly advising several of Pitt's iGEM teams, saw the potential to combine their respective expertise in a new research project as well.
“Jason is an expert in cell engineering and immunology and has a long track record in that, and my expertise is in synthetic organic chemistry and chemical biology,” Deiters said.
The pair set their sights on CAR T-cell therapy, a type of immunotherapy where a patient’s own immune cells are engineered to attack cancer cells. It’s an approach that’s found strong and lasting success in treating blood cancers like leukemia, but solid tumors have proven more difficult to crack. Delivering the altered cells to the right parts of the tumor at the right time requires a kind of flexibility that isn’t yet available on that market.
That’s just what Monarch offers. Lohmueller describes their platform as a Swiss army knife: By separating the part of the cell surface receptor that recognizes cancer cells from the part that activates the CAR T cells, it allows researchers to reprogram T cell targeting to different tumors. And making use of powerful covalent bonds between components allows the use of a broad range of small molecule-based targeting motifs called “adaptors.”
Together, that means more flexibility and precision in treating tumors, with potentially reduced side effects.
“We’re trying to make the adaptors orally available eventually, so patients could take them at home, and they wouldn’t have to come to a physician’s office for an infusion,” Deiters said. “And that, paired with the much lower manufacturing cost of small molecules, will hopefully then drive down the cost of these very expensive therapies.”
Pitt is ranked No. 14 nationally for U.S. patents, with 114 in the past year alone. Over the past seven years, the University has spun out 109 companies from Pitt technologies.
Want to be one of them? If you are a Pitt faculty, staff or student with an interest in pursuing commercialization of a business idea or research innovation, contact the Office of Innovation and Entrepreneurship at innovate [at] pitt.edu.
Out of the lab
Now their time is split between pushing their research forward — studying ways to attack multiple tumor cell targets at once and advancing their research to new animal models — and finding ways to scale up manufacturing of the product as they work toward a phase one clinical trial.
Along the way they’ve sought assistance from Pitt’s Innovation Institute, working with Andrew Remes to license their technology and entrepreneur in residence Dan Broderick to help them navigate the startup ecosystem, as well as Paul-Valentin Pitou from the Office of Industry and Economic Partnerships (also a part of the Office of Innovation and Entrepreneurship) to explore industry partnering opportunities.
“They’ve been really helpful for getting us started in the process, obviously for filing [intellectual property] protection, and then looking at different models for establishing a business or licensing,” Lohmueller said.
The pair were then able to gather a team that included experts with long careers in cell therapy and manufacturing, including CEO Christopher Potts, and officially launched Monarch Therapeutics in December 2023.
In a field like immunotherapy, where bringing therapies to patients is an expensive, yearslong process, Lohmueller said he always saw a future where he was involved in commercializing technology. But actually doing it is a shift that’s worked its way into everything the duo does, altering the way they plan studies and picture the broad strokes of their research efforts.
“You’re more focused on helping patients — the bar is higher, and the thought process is slightly different. It directs, in very subtle ways, the way you think about your next experiment,” said Deiters. “The goal here is not a publication, right? The goal is a revolutionary therapy that will improve patients’ lives.”
Photography by Tom Altany