Imagine developing a first-of-its-kind therapy that saved the life of one woman dying from colon cancer, only to lose the financial backing needed to bring it to market.
That's the reality for University of Minnesota researchers who were excited last week to report early-stage results of their genetically edited immunotherapy, which halted tumor growth for a month or two in several patients and reversed cancer symptoms in one Minneapolis woman.
Intima Bioscience celebrated the results, which were featured at a national cancer research conference. But the startup company had already pivoted to other experimental therapies that could be faster, cheaper to make, and target more types of cancer.
U researchers are partnering with Intima on those cancer-fighting alternatives, but are assembling a "Minnesota homegrown" team to keep their studies of the colon cancer therapy going.
"They found it too costly and complex, but we've been working to make it more affordable, more rapid, more potent," said Branden Moriarity, co-director of the U's Center for Genome Engineering. "We are doubling down on this therapy."
The experimental treatment has been several years in the making. U researchers used CRISPR gene-editing to deactivate a gene, called CISH, in tumor-fighting white blood cells and improve their ability to recognize and attack cancer.
"We believe that CISH is a key factor preventing T cells from recognizing and eliminating tumors," Moriarity said.
The U-led trial was the second to receive federal approval for human testing of a CRISPR-edited cell therapy, Moriarity said. The goal was to prove that a small group of patients with severe cancers could safely tolerate the therapy, before testing its effectiveness in a larger group and then pursue approval by the U.S. Food and Drug Administration.
Emma Dimery said she was out of options when offered a chance to join the trial three years ago. The Minneapolis woman had received radiation, chemotherapy and surgeries to slow the growth of her cancer, which started in her colon but had spread by the time it was detected.
Her youth had helped her survive — she was 23 at the time of her diagnosis in 2013 — but she was starting to face her own mortality a decade later.
"Right before the trial, that was my lowest point," she said. "I was starting to have to wrap my mind around that idea, because I didn't have any more treatment options available."
Experimental treatments are often reserved for the sickest patients, because their possible benefits at that point outweigh unknown risks.
Twenty-two cancer patients were selected for the U trial, but it took more than three months to harvest and modify their own immune cells and then produce enough for an effective therapy. Ten patients died or had complications that prevented their participation before their customized therapies were ready.
Of the 12 who participated, half saw a one-month delay in their tumor growth, while some experienced two-month delays. All eventually died from their aggressive cancers except Dimery.
One month after the treatment in 2023, an imaging scan showed her tumor had shrunk in half. By two months, it was gone. Now, she said, she only needs imaging scans every other year to make sure the cancer doesn't return.
"I don't even have words to describe how incredible that is," she said. Bad news is common for end-stage cancer patients, but she always hoped a cure would come along if she could hang on.
Leaders at Intima balanced the positive outcomes against the cost of generating custom-made cellular therapies. Each patient in the trial cost hundreds of thousands of dollars.
The New York-based company is hoping instead to use its discoveries from this study to develop other therapies that don't take as much time and money.
The U researchers are hoping to learn more about what worked, and what didn't, in their trial. Genetic differences among the patients could explain why some had more success, and why Dimery experienced a complete reversal.
The researchers are starting from scratch, in some respects, hoping they can create a new genetically modified therapy that takes weeks instead of months to produce, and at less than $100,000 per patient.
"We are hoping to cut it by basically one third of the time, around a month," said Beau Webber, a U assistant professor and cancer researcher. "We've worked up some ways to do that, and on top of that improve the efficacy."
The gene editing targets tumor-infiltrating lymphocytes (TILs), which are white blood cells that the body naturally produces in response to cancer. The gene therapy "hardwires" the cells to be better cancer-fighters, meaning that it only has to be administered once, Webber said. Other therapies require continuous or follow-up treatments.
The researchers have pieced together funding from the university and grants from the Department of Defense and philanthropic organizations to continue pursuing the cell therapy. They teamed up with colleagues from Mayo Clinic to explore whether the approach works against other cancer types as well.
Dimery, now 35, said she wants others with end-stage cancers to feel the same joy she encountered when her cancer reversed. After a decade tethered to clinic appointments and hospital visits, she is making plans with her husband to travel. She enjoys gardening at their new home in south Minneapolis.
A graduate of the Minnesota College of Art and Design, she works at an art supply store in Edina and is building a freelance illustration business. She was anonymously identified as Patient 22 in records of the U study, and plans to work that into a tattoo to remember what she endured.
Dimery suffered persistent pain related to her cancer, but that has faded so much that she recently weaned off the painkillers she took for years. She still experiences flareups, but is glad to be off the medications.
"Nothing I can't handle with Tylenol," she said.
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