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NIH scientists have a cancer breakthrough. Layoffs are delaying it.

Scientists at the National Institutes of Health demonstrated a promising step toward using a person’s own immune cells to fight gastrointestinal cancers in a paper in Nature Medicine on Tuesday, the same day the agency was hit with devastating layoffs that left many NIH personnel in tears.

The treatment approach is still early in its development; the personalized immunotherapy regimen shrank tumors in only about a quarter of the patients with colon, rectal and other GI cancers enrolled in a clinical trial. But a researcher who was not involved in the study called the results “remarkable” because they highlight a path to a frustratingly elusive goal in medicine - harnessing a person’s own immune defenses to target common solid tumor cancers.

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Until now, cell-based immunotherapy has worked mainly on blood cancers, such as leukemia, but not the solid cancers that seed tumors in the breast, brain, lungs, pancreas and GI tract.

“I think this is a very exciting study,” said Patrick Hwu, president of the Moffitt Cancer Center in Tampa, Florida. “There’s still a lot of work to do … but this is a really great start in the right direction.”

But the progress arrives at a sad time for science - and for patients, said the leader of the work, NIH immunotherapy pioneer Steven Rosenberg.

Two patients’ treatments using the experimental therapy had to be delayed because NIH’s capacity to make personalized cell therapies has been slowed by the firing of highly skilled staff and by purchasing slowdowns. Those occurred even before major layoffs took place Tuesday.

The quality of care at the NIH Clinical Center, the country’s largest research hospital, remains excellent, Rosenberg said. But the administration’s aggressive downsizing of staff and hampering of routine activities is beginning to delay that care.

“Everything I try to do, I try to do at warp speed. These are people with desperate illnesses and nowhere to go,” Rosenberg said. “Right now, assuming things don’t get any worse, it would be a month [delay]. These are not patients that have very many months left.”

Natalie Phelps of Bainbridge Island, Washington, is one of those who can’t wait. The 43-year-old mother of two learned five years ago that GI symptoms that her doctors had attributed to her second pregnancy were actually caused by colorectal cancer.

Since then, Phelps has been through “pretty much any hell I can go through” - an 18-hour surgery to remove her initial tumor, radiation to her brain, three liver surgeries and 48 rounds of chemotherapy. Still, the cancer spread through her body.

This fall, she felt hope when she arrived at the NIH Clinical Center in Bethesda, Maryland, for two days of intensive testing to determine whether she qualified for one of Rosenberg’s trials. She marveled at the quality of the medical care and the efficiency of the work.

“When I was invited out, just to be screened, I was overjoyed. I felt like I won the jackpot,” Phelps said. “Walking into the NIH … it just made me so proud - it was such a beautiful building and everything was managed so professionally and efficiently, in a way that I hadn’t experienced at any health-care institute around the country.”

HHS responded to an email asking about clinical trial delays with a statement: “NIH and HHS are complying with President Trump’s executive order.”

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Progress builds over years

For decades, scientists have dreamed of harnessing patients’ own immune cells to attack cancers. Rosenberg has long been a leader in this field, at the very cutting edge of medicine.

In 2017, the first drug in a transformative new class of medicine - one based on immune cells harvested from patients’ blood and genetically engineered to target cancer cells - was approved to treat blood cancers.

Last year, a different type of cell-based immunotherapy was approved for melanoma that has spread to other parts of the body or resisted other forms of treatment. Instead of engineering the cells, scientists harvest and expand cancer-attacking immune cells taken from patients’ own tumors - called TILs, short for tumor infiltrating lymphocytes. Those cells are normally present, but not in large enough numbers to slow down the cancer.

Rosenberg’s work has driven both approaches to cancer therapy forward. But despite the advances, finding ways to tailor this cell-based immunotherapy approach to common solid tumors that cause the vast majority of cancer deaths has remained a major scientific challenge.

“Very rarely does research work in a straight line - you have ideas, you pursue them, most things do not work, some things do work. You build upon them,” Rosenberg said.

That’s what happened in the new study. Rosenberg and colleagues first tried to create TILs using the method that worked in melanoma for 18 patients with GI cancers that had spread. It failed completely.

In a second iteration, his team sequenced the mutations present in each patient’s tumor and used that information to sift out and expand the TILs that could home in on that patient’s specific tumor cells. The results were far from a triumph, but provided a clue - this time, three of 39 patients’ tumors shrank.

In the last stage of the trial, the scientists added a drug called pembrolizumab that takes the brakes off immune cells. This time, eight of the 34 patients responded.

“Right now, only a few labs in the country can do what they just did,” Hwu said.

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Patients who can’t wait for progress

Rosenberg is already working to refine and improve upon the results. But he said that in his many decades of cancer research, he has never seen anything like the turmoil outside his lab, which is beginning to affect the science.

Two scientists involved in the specialized process of preparing cells for patients’ treatments were fired in the probationary purge. Nine highly skilled scientists on his team have appointments that need to be renewed in 2025 or early 2026, but with no assurance they will be.

“If they are not, that will set us back more,” Rosenberg said. “We’ve had to slow down our work and delay the treatment of some patients.”

Even more-minor restrictions are throttling progress. Travel is restricted by an administration order, so Rosenberg couldn’t attend a meeting of the Society of Surgical Oncology where physicians and scientists exchange ideas that move cancer care forward.

After the probationary firings, the number of people capable of purchasing materials essential for research has plummeted, making it slower and more difficult to obtain supplies. Rosenberg is now worried that the massive reduction in force last week will make the process even more onerous.

When Phelps went to NIH, she told her young children she was going to visit the best doctors in the country to see if they had a solution. Those doctors told her she was a good candidate for the TIL trial, with one caveat - she needed to wait for one of the many tiny tumors in her body to grow large enough to meet the minimum size criteria.

She went home, where she has been anxiously waiting for her tumors to grow large enough to qualify for the trial. Now, she has a new source of fear: The changes the new administration has imposed have dampened her hope for the future.

“It’s one thing that seems unfair: Why would a metastatic cancer patient need any more stress?” Phelps said. “Why slow down the research when cancer rates are on the rise, particularly with young people under 50?”