The Daily Populous Thursday March 19th, 2026 night edition
Authored by sciencedaily.com and submitted by hard2resist

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.

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 patients achieved a complete response, meaning all detectable cancer disappeared.

The two patients whose cancer vanished had melanoma and breast cancer, respectively. Both cancers are known for being aggressive and prone to recurrence.

"The melanoma patient had dozens of metastatic tumors on her leg and foot, and we injected just one tumor up on her thigh," Ravetch says. "After multiple injections of that one tumor, all the other tumors disappeared. The same thing happened in the patient with metastatic breast cancer, who also had tumors in her skin, liver, and lung. And even though we only injected the skin tumor, we saw all the tumors disappear."

Immune Cells Transform the Tumor Environment

Samples taken from treated tumors revealed how strongly the immune system responded.

"We were quite surprised to see that the tumors became full of immune cells -- including different types of dendritic cells, T cells, and mature B cells -- that formed aggregates resembling something like a lymph node," Osorio says. "The drug creates an immune microenvironment within the tumor, and essentially replaces the tumor with these tertiary lymphoid structures."

These structures, known as tertiary lymphoid structures (TLS), are often linked to better outcomes in cancer treatment and stronger responses to immunotherapy.

Researchers also detected TLS in tumors that were not directly injected with the drug.

"Once the immune system identifies the cancer cells, immune cells migrate to the non-injected tumor sites," Osorio explains.

Larger Trials Aim to Improve Cancer Immunotherapy

The promising findings have led to additional clinical trials. Ravetch's group is now collaborating with scientists at Memorial Sloan Kettering and Duke University to further evaluate the therapy.

Current phase 1 and phase 2 trials are testing 2141-V11 against several difficult-to-treat cancers, including bladder cancer, prostate cancer, and glioblastoma. Nearly 200 patients are participating across these studies.

Researchers hope the larger trials will reveal why some patients respond to the treatment while others do not, and how response rates might be improved.

For instance, the two patients whose cancer disappeared both showed high clonality of T cells when the trial began. These immune cells are key players in killing cancer.

"This suggests there are some requirements from the immune system in order for this drug to work, and we're in the process of dissecting these characteristics in more granular detail in these larger studies."

Understanding these factors could help researchers predict who will benefit from the therapy.

"As a general rule, only 25 to 30% of patients will respond to immunotherapy, so the biggest challenge in the field is to try to determine which patients will benefit from it. What are the indicators or predictors of response? And how can we convert non-responders into responders?"

sonofeevil on March 18th, 2026 at 11:02 UTC »

This was done a while back in Australia. A company called Viralytics.

They injected large cell tumors with a strain of influenza which basically put a laser target onto the cancer for the bodies immune system. The drug was called Cavatak.

Then combined with immune response boosters in trials they expected it to eliminate that tumour but what it did was eliminate ALL cancer cells, not just the one they injected.

The clinical trials were done on treatment resistant Stage 3 and Stage 4 cancers which saw a 60% remission rate which is basically a fucking miracle drug.

The company was brought by Merck and was the largest pharmaceutical acquisition in Australia history at $502 million.

Merck then shelved Cavatak.

They brought the company to bury the drug.

https://hmri.org.au/news-and-stories/uon-biotech-firm-sells-502-milion/

https://pmc.ncbi.nlm.nih.gov/articles/PMC4288429/&ved=2ahUKEwjp4OeKpamTAxXr2TQHHStYLI8QFnoECBsQAQ&usg=AOvVaw02xNIMrTFpaJL7oSA6SINs

Here's a link where Merck announced they were shelving it but didn't say why

https://www.fiercebiotech.com/biotech/merck-ditches-cavatak-more-four-years-after-buying-viralytics

Edit: a partner of mine used to work for the company and I went to their Christmas party quite a few years back and got to talk to the owner and researcher who developed the drug and he was such a lovely person and so passionate about what he'd made. I imagine it really upsets him to see what has become of it.

He and his research partner went on to take the money and reinvest it into Malaria research.

Fireblaster2001 on March 18th, 2026 at 10:14 UTC »

There is a phenomenon known to happen spontaneously, but rarely, called the abscopal effect, where treatment of a localized tumor will cause the immune system to ramp up and go after metastasis all on its own.

If they figured out how to purposely cause this, then that frickin rules!!

Ignorant_Ismail on March 18th, 2026 at 10:06 UTC »

It's very early in clinical trial phases, hence the small sample size. Nevertheless, it looks very promising. It seems to wake up the adaptive cells of our immune system, something cancer cells with their various cell surface receptors try to evade and decrease their activation. The wake up of adaptive cells helps promote release of various signaling molecules that promote recognition and clearance of the cancer. Since many of cancer cells share similar properties, the immune cells with their new training are able to remove the cancer cells that metastasized to various parts of the body. It's very good research and I hope it ultimately helps patients with solid tumors