Scientists inject one tumor and watch cancer vanish across the body
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Scientists inject one tumor and watch cancer vanish across the body
A revamped cancer immunotherapy triggered whole-body tumor destruction in early trials—shrinking cancers in half of patients and wiping them out entirely in two.
Date:
March 16, 2026
Source:
Rockefeller University
Summary:
A redesigned cancer immunotherapy is showing striking early results after decades of disappointment with similar drugs. Researchers engineered a more powerful CD40 agonist antibody and changed how it’s delivered—injecting it directly into tumors instead of into the bloodstream. In a small clinical trial of 12 patients with metastatic cancers, six saw their tumors shrink and two experienced complete remission.
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A redesigned CD40 immunotherapy delivered directly into tumors triggered powerful immune responses in a small clinical trial, shrinking tumors in half the patients and completely eliminating cancer in two. Even tumors that weren’t injected disappeared, hinting that the treatment can spark a body-wide immune attack. Credit: AI/ScienceDaily.com
For more than two decades, scientists have explored a group of cancer drugs known as CD40 agonist antibodies. Early experiments suggested these treatments could strongly activate the immune system and help it destroy cancer cells. However, results in people were disappointing. Clinical trials showed only modest benefits, and the drugs often caused serious side effects such as widespread inflammation, dangerously low platelet levels, and liver damage. These reactions occurred even at relatively low doses.
In 2018, researchers led by Jeffrey V. Ravetch at Rockefeller University reported a potential breakthrough. The team redesigned a CD40 agonist antibody to improve its effectiveness while reducing harmful side effects. Their work relied on specially engineered mice that mimic key immune pathways found in humans. The encouraging findings suggested the therapy might work better in people if delivered differently.
The next step was testing the drug in patients.
Early Clinical Trial Shows Tumor Shrinkage and Remission
Results from the phase 1 clinical trial of the modified drug, called 2141-V11, have now been published in the journal Cancer Cell. Among the 12 participants in the study, tumors shrank in six patients. Two of those patients experienced complete remission, meaning their cancers disappeared entirely.
"Seeing these significant shrinkages and even complete remission in such a small subset of patients is quite remarkable," says first author Juan Osorio, a visiting assistant professor in Ravetch's Leonard Wagner Laboratory of Molecular Genetics and Immunology and a medical oncologist at Memorial Sloan Kettering Cancer Center.
Researchers also observed something unusual. The treatment did not only affect the tumors that were injected with the drug. Tumors located elsewhere in the body also shrank or were eliminated by immune cells.
"This effect -- where you inject locally but see a systemic response -- that's not something seen very often in any clinical treatment," Ravetch notes. "It's another very dramatic and unexpected result from our trial."
How the Engineered CD40 Antibody Works
CD40 is a receptor found on the surface of certain cells and belongs to the tumor necrosis factor (TNF) receptor superfamily. These receptors are mainly present on immune cells. When CD40 is activated, it signals the immune system to mount a stronger response, helping trigger anti-tumor immunity and generate cancer-targeting T cells.
In 2018, Ravetch's team engineered the antibody 2141-V11 with support from Rockefeller's Therapeutic Development Fund, founded by trustee Julian Robertson and continued by the Black Family Foundation. The redesigned antibody binds tightly to human CD40 receptors and was modified to improve crosslinking by interacting with a specific Fc receptor. Laboratory studies showed the new design was about 10 times more effective at triggering an immune attack against tumors.
Researchers also changed how the drug was delivered. Traditionally, CD40 therapies were given through intravenous infusion. Because CD40 receptors exist throughout the body, many healthy cells would absorb the drug, leading to toxic side effects.
Instead, the team injected the treatment directly into tumors.
"When we did that, we saw only mild toxicity," Ravetch says.
These findings laid the groundwork for the phase 1 clinical trial, which aimed to determine a safe starting dose and better understand how the therapy works in patients.
Tumors Disappear in Some Patients
The trial involved 12 people with several types of metastatic cancer, including melanoma, renal cell carcinoma, and different forms of breast cancer. None of the participants experienced the severe side effects previously associated with CD40 drugs.
Six patients showed tumor shrinkage throughout the body. Two