A new, highly sensitive cell therapy was able to wipe out three different kinds of solid tumors in mice, an important advance in an area where CAR-T cells have long struggled. But significant regulatory red tape stands in the way of progress, two leaders in the field told Fierce.
The findings, published in Science on Feb. 26, come from the Columbia University research lab of Michel Sadelain, M.D., Ph.D., a pioneer in CAR-T cell therapy.
Since its first successful use in leukemia in 2010, CAR-T therapy—where T cells are taken from a patient, engineered to fight the cancer and then being reinfused—is now a mainstay of care for blood cancers. But scientists have struggled to adapt the medicines to treat solid tumors for multiple reasons.
Sadelain’s new approach overcomes one challenge by homing in on CD70, a receptor protein found in such low levels on many cancer cells that it was previously thought to not be present at all. The technique was able to eradicate tumors that were taken from patients with kidney, pancreatic and ovarian cancers and grafted onto mice. This solves one historic problem for solid tumor CAR-T—that many tumor cells don’t share a common target. But other roadblocks remain.
“There are tumors that impede the entry of T cells,” Sadelain told Fierce Biotech. “Some are very smart. There's many, many layers of defense that they can put up against the immune system.”
Adding to the biological hurdles is regulatory red tape, not helped by intense leadership turnover at the FDA and requirements much more onerous than those found in rising rival China.
Transforming CAR-T into effective solid tumor treatments will require multiple new feats of cellular engineering, Carl June, M.D., another CAR-T pioneer at the University of Pennsylvania, told Fierce. This includes expanding the range of targets the cells can pursue and making sure the CAR-Ts can penetrate and survive inside tumors. But the FDA requires that each of these novel techniques be tested in clinical trials one at a time, rather than in parallel.
“That's one of the reasons China is eating our lunch now,” June explained. “They can do more rapid testing at early-stage trials of novel concepts,” while the U.S. system demands a “very slow run-in test of each individual component before you could get to the one you think that actually works.”
June raised the exact same concerns earlier in the second Trump administration, during a June 2025 FDA roundtable on cell and gene therapies. At that event, health leaders pledged that they would slash red tape at the FDA, with Health and Human Services Secretary Robert F. Kennedy, Jr., asking attendees for a list of “any regulations you think we ought to be getting rid of.”
Sadelain agrees that testing combined innovations is cumbersome under FDA regulations, but that’s not the only burden weighing down the CAR-T field. Manufacturing standards for the therapies are much higher in the U.S. than in China or Australia, he told Fierce, which significantly raises costs.
Removing the need for experimental CAR-Ts to meet these good manufacturing practices at early stages, while still using ingredients that are sterile and research-quality, would drastically lower the price of trials without compromising patient safety, Sadelain said.
“It takes so much time to gear up for these trials, and it costs so much money, that you have 10 good ideas and you can do one trial,” he said. “Nobody wants to lower safety standards to the point that they pose undue risks, of course, but on the other hand, you can't choke the field by placing hurdles that are maybe higher than need be.”
Reached for comment, an FDA spokesperson highlighted the recent approval of BMS’ CAR-T Breyanzi (liso-cel) in marginal zone lymphoma.
“The FDA continues to optimize its regulatory authority to expand treatment options in the fight against cancer,” the spokesperson said. “FDA is strongly committed to advancing cell therapies to meet the needs of patients with rare cancers.”
For now, Sadelain is forging ahead even with the knowledge of the obstacles ahead. With CD70 not very common in healthy cells and safety signals looking good so far, his team is now working on the manufacturing process for the new CAR-T cells and trying to raise funds for a human trial, he told Fierce.
Heat-seeking missile
Many solid tumors are so-called “cold” tumors that erect barriers keeping the immune system out. But even if a tumor is “hot,” and the body’s immune cells can penetrate into the tumor microenvironment, they are met with hostile conditions and a diverse swath of cancer cells that often don’t share a common target.
“A tumor is a collection of cancer cells, but it's more than that,” Sadelain said. “It's a whole little universe that is created around the tumor,” complete with blood vessels to help the tumor grow.
If it gets inside a tumor, a CAR-T cell must contend with different enemies that don’t all share surface molecules like CD19, which was the first target successfully attacked with CAR-T cell therapy.
“We identified CD19 years ago, and we can now say that was a good target to pick,” Sadelain recalled. But while extremely effective for blood cancers, CD19 isn’t found on all solid tumor cells, and that’s where it fails as a target, he added.
With solid tumors, “we don't have the lineage-specific dream antigens like BCMA and CD19 in blood cancer,” Penn’s June agreed. “That's been a major problem.”
One molecule sometimes found dotting the surface of tumor cells is CD70, but like CD19, it was thought to be present only on some cells and not others. But when Sadelain’s team took a closer look at images of tumor cells, they found hints that CD70 was actually almost always there—just at very low levels that can’t be detected by normal methods.
With CD70 showing promise as a “dream antigen” for certain solid tumors, the question then became how to target it effectively. The receptor is at such low levels on some cells that normal chimeric antigen receptors—the CARs of CAR-T—can’t bind to them. So Sadelain’s team turned to CRISPR, a tool that didn’t exist when CAR-T therapy was first developed, to engineer a more sensitive targeting tool.
The researchers opened up the T cell’s genome and added a CD70-seeking component to the T cell receptor, which Sadelain said “can detect 10 to 50-fold fewer molecules” than a CAR. Normally, T cell receptors can only detect a target if it is bound to a specialized complex called HLA on the surface of a different cell; this is no good for making a therapy because HLAs differ dramatically from person to person.
The new approach removes this limited T cell receptor and swaps in one that is HLA-independent, making any target on the surface of a cell fair game.
“They can recognize antigens in a completely different way,” Sadelain said of the modified T cell receptors. Sadelain’s team calls them HLA-independent T cell receptors, or HITs, and he considers them part of the broader CAR family.
HITs are just one of numerous innovations in how scientists are tweaking CAR-T cells to combat solid tumors. Many, including June, are pursuing dual-targeting CARs designed to eliminate a greater portion of tumor cells than a single-targeting approach alone. His CAR-T company, Tmunity, acquired by Gilead’s Kite Pharma in 2022, is trying this method for glioblastoma, he said.
June also has another biotech, Dispatch Bio, that aims to turn cold tumors hot by triggering them with viruses, so they become susceptible to immune-based therapies like CAR-T.
And donor-derived CAR-T company Allogene Therapeutics is also after CD70, with a candidate currently in a phase 1 trial for renal cell carcinoma.
Despite the regulatory challenges facing solid tumor CAR-T, both Sadelain and June are optimistic when it comes to the science. June highlighted prostate cancer, especially, where his group is running their own academic trials and both AstraZeneca and Johnson & Johnson have CAR-Ts in development.
“There are multiple obstacles to the efficacy of these cells in solid tumors, and I think that's why people are optimistic,” Sadelain said. “Once you start understanding the problem, you're going to find solutions to overcome it.”