SEOUL= By blocking TGF-β only inside tumors, an experimental therapy cleared pancreatic and breast cancers in mice and left lasting immunity that reached other cancer types
Many solid tumors, including many cancers of the pancreas, breast, brain and lung, protect themselves with a dense wall of scar-like tissue. That wall keeps the immune system's cancer killing T cells out. It is a major reason why immunotherapy drugs, which have transformed treatment for some patients, help only a minority of people with solid tumors.
A study published in Cancer Cell describes an experimental drug that breaks down this barrier from inside the tumor and lets T cells in to attack. In mice, the drug cleared aggressive pancreatic tumors, stopped breast cancer from spreading, and left the animals with long-lasting immune memory. That memory protected against new tumors, including some different types of cancer.
The international study was led by Dr. Seong-Jin Kim and his team of scientists at MedPacto, Inc., in Seoul, Korea. Co-author John J. Letterio, MD, PhD, is Director of the Angie Fowler Adolescent and Young Adult Cancer Institute at University Hospitals Rainbow Babies & Children's Hospital and Director of the Developmental Therapeutics Program at Case Comprehensive Cancer Center, Case Western Reserve University.
One molecule behind the wall
Tumors flood their surroundings with a signaling molecule called TGF-β. In solid tumors of many kinds, it directs nearby support cells to build fibrous tissue, and it suppresses the immune cells that could attack the cancer.
Biopharmaceuticals that block TGF-β throughout the body have disappointed in clinical trials. Safe doses don't block enough of it inside the tumor, and higher doses disrupt TGF-β's normal roles in healthy tissue.
A drug that finds the tumor
The team engineered a TGF-β blocker, called FEBP-sTβRII, with a tag that sticks to a form of the protein fibronectin that is abundant in tumors but rare in healthy adult tissue. The researchers found this target at high levels in mouse models of breast, lung, liver, prostate, pancreatic and brain cancers and melanoma, and in many human tumor types. Because so many cancers share it, the approach could apply across many solid tumors.
The drug gathers in the tumor and stays there for days. The same blocker without the tag had little effect on tumors. It also changed the activity of 693 genes in the blood, compared with just 25 for the targeted drug.
Turning the tumor's neighborhood against the cancer
Once the barrier loosened, killer T cells moved into the tumor. They released a signal called interferon-gamma that converted the tumor's own support cells and nearby immune cells into allies. These cells began displaying pieces of the cancer to the immune system, fueling a self-reinforcing attack. The team saw this reprogramming in both pancreatic tumors and melanoma.
This is a distinct way to switch on tumor immunity. Current immunotherapies release the brakes on T cells. This approach also rebuilds the environment around the tumor so the immune system can reach the cancer and recognize it.
Results across cancer types
"TGF-β helps build the defenses of many solid tumors, so this approach has the potential to reach well beyond a single cancer," said Dr. Letterio. "By delivering the blocker directly to the tumor, we don't just open the door to T cells. We appear to be teaching the immune system lessons it remembers long after the tumor is gone, and in some cases those lessons protect against other cancers."
What comes next
The findings point to a strategy for solid tumors that resist current immunotherapy, alone or in combination with existing immunotherapy drugs. The immune pattern the drug created in mice resembles patterns seen in patients who responded to immunotherapy for melanoma, gastric cancer and pancreatic cancer. Measuring the drug's target in a patient's tumor could help identify who is most likely to benefit.
"This study shows that where you block TGF-β matters as much as whether you block it," said senior author Seong-Jin Kim, PhD, of MedPacto.
A version of the drug designed for humans has entered safety testing, with clinical trials planned for 2027. These human trials are designed to demonstrate whether the drug is safe and effective in patients with solid tumors refractory to other, standard therapies.
Contact: minhoo.jang@medpacto.com
Cancer Cell
Experimental study
Animals
A stroma-sensing TGF-β blockade reprograms CAF-myeloid niches to induce durable tumor immunity
9-Nov-2026
No conflict of interest