Preclinical Findings Show Experimental Drug Eliminates 75% of Aggressive Pancreatic Tumors and Enhances Immune System Memory to Fight Other Cancers
By blocking TGF-beta only inside tumors, an experimental therapy cleared pancreatic and breast cancers in mice and left lasting immunity that reached other cancer types
November 9, 2026
CLEVELAND, Ohio — Many solid tumors, including many cancers of the pancreas, breast, colon 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 today 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.
Drugs 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, colon, 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
- Pancreatic cancer: The drug worked in three different mouse models. In one aggressive model, tumors disappeared in 75% of treated mice, and seven of eight were still alive 270 days after treatment ended.
- Triple-negative breast cancer: In a highly metastatic model, the drug slowed tumor growth, prevented spread to the lungs and extended survival. Standard immunotherapy and untargeted TGF-β blockers gave little or no benefit.
- Combination therapy: Added to an existing immunotherapy drug (anti-PD-1), it nearly eradicated pancreatic tumors that resist that drug alone.
- Lasting memory: Cured mice rejected the same cancer when it was reintroduced months later. Many also rejected bladder and lung tumors they had never encountered.
- Transferable protection: T cells from cured mice protected cancer-free mice against bladder cancer.
"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 and the GILO Institute.
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.
About the study
"A Stroma-Sensing TGF-β blockade reprograms CAF–myeloid niches to induce durable tumor immunity," Cancer Cell. First author: Dong Woo Kang, PhD, MedPacto. Senior author: Seong-Jin Kim, PhD, MedPacto and GILO Institute. Funding: Korea Drug Development Fund, Republic of Korea.
Disclosures: Dr. Kim is a founder of MedPacto and co-founder of Celloram. Dr. Letterio is a co-founder of Celloram and a member of MedPacto's clinical advisory board. MedPacto holds pending patents on the drug.
About University Hospitals / Cleveland, Ohio
Founded in 1866, University Hospitals serves the needs of patients through an integrated network of 21 hospitals (including five joint ventures), more than 50 health centers and outpatient facilities, and over 200 physician offices in 16 counties throughout northern Ohio. The system’s flagship quaternary care, academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, Northeast Ohio Medical University, Oxford University, the Technion Israel Institute of Technology and National Taiwan University College of Medicine. The main campus also includes the UH Rainbow Babies & Children's Hospital, ranked among the top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, with more than 3,000 active clinical trials and research studies underway. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including “America’s Best Hospitals” from U.S. News & World Report. UH is also home to 19 Clinical Care Delivery and Research Institutes. UH is one of the largest employers in Northeast Ohio with more than 30,000 employees. Follow UH on LinkedIn, Facebook and Twitter. For more information, visit UHhospitals.org.
About University Hospital Rainbow Babies & Children’s / Cleveland, Ohio
UH Rainbow Babies & Children’s is Northeast Ohio’s most expansive pediatric care network, with more than 587,000 annual patient visits across 60 locations. Anchored by nationally ranked UH Rainbow Babies & Children’s Hospital – home to a Level I Pediatric Trauma Center – our team of 280+ physicians provide leading-edge care across 19 medical divisions and 9 surgical specialties. As an academic medical center affiliated with Case Western Reserve University School of Medicine, UH Rainbow is a hub for innovation, research, and training. In close partnership with UH MacDonald Women’s Hospital, our experts deliver seamless, family-centered care from pregnancy through childhood, ensuring healthier beginnings and brighter futures for kids across the region.