Two Cancer Immunotherapy Efforts Target T-Cell Failure: One in Lab Dishes, One in a Single Patient

Immunotherapy works until it doesn't. Two separate research efforts, one from UCLA and one from an Israeli biotech, are going after that problem from different angles. Neither has shown that it helps a cancer patient live longer.

UCLA: keeping engineered T cells from burning out

Researchers at the UCLA Health Jonsson Comprehensive Cancer Center found that temporarily boosting a protein called p53 helped specially prepared immune cells stay stronger and kill more melanoma cells in laboratory experiments. The study was published in Frontiers in Immunology.

The target is T cells, the immune cells that help the body fight disease. Some cancer treatments take a patient's T cells, modify them in a lab so they can recognize cancer, and return them to the body to attack tumors.

The weak point is exhaustion. The UCLA researchers said these cells can eventually wear down and become less effective at fighting cancer.

To address that, the team treated human T cells with an experimental drug called navtemadlin, which temporarily increases the activity of p53, a protein known for helping prevent cancer. The treated cells showed fewer signs of exhaustion, had more energy and developed characteristics that could help them last longer. Against melanoma cells in the lab, they were significantly more effective at killing than untreated T cells, according to the research.

Kien Vuu, a Los Angeles-based physician and former UCLA assistant clinical professor who was not involved in the work, confirmed exhaustion is one of the biggest challenges in these treatments. "After repeated encounters with cancer, they become 'exhausted' and lose their ability to multiply and attack," he told Fox News Digital.

Vuu said the appeal is simplicity. "Rather than adding another genetic modification, this approach adds a drug during the manufacturing step, when a patient's T cells are being prepared in the lab," he said. If further research bears it out, he said, it could help T cells stay effective longer, particularly against solid tumors.

The findings are still preliminary. The experiments were done on cells in a lab, not in patients.

Biond: a first-in-class antibody enters human testing

On Monday, Nov. 9, Biond Biologics Ltd., a private clinical-stage company based in Misgav, Israel, announced that the first patient had been dosed in a first-in-human Phase 1 trial of BND-67 in advanced solid tumors.

BND-67 is an antibody designed to prevent CD28 shedding. CD28 is a receptor involved in T-cell activation. The company says blocking its shedding is meant to preserve normal CD28 signaling and boost the anti-tumor immune response without the systemic toxicity tied to CD28 agonism. Biond describes a dual mechanism: it enhances effector T-cell activity while reducing regulatory T-cell differentiation.

The trial targets a specific group: patients who relapsed after earlier clinical benefit from immune checkpoint therapy. Each patient first gets BND-67 alone, then BND-67 combined with an anti-PD-1 drug.

The first patient was treated at the Davidoff Center at Rabin Medical Center in Israel, one of several planned sites. Biond said that patient completed the 0.3 mg/kg monotherapy phase with no dose-limiting toxicities or infusion-related reactions. The patient is now receiving BND-67 with nivolumab every two weeks.

"Patients who relapse after responding to immunotherapy represent a significant unmet medical need," said Professor Salomon Stemmer, head of research, development and innovation at the Davidoff Center and a trial investigator.

Giovanni Selvaggi, Biond's chief medical officer, called it "an entirely new therapeutic avenue for cancer immunotherapy" and said the 0.3 mg/kg dose "was shown to be safe and tolerable with sustained receptor occupancy."

That is the company's own account of one patient at the lowest reported dose. Phase 1 trials exist to test safety and find a workable dose, and this one also tracks preliminary anti-tumor activity. A clean first dose is a starting point.

What the two share, and what separates them

Both efforts aim at the same bottleneck: immune cells that start strong and then stop working. UCLA tries to fix it while the cells are being manufactured outside the body. Biond is trying to fix it inside the patient with an antibody.

They are also at different stages. UCLA's result comes from lab experiments on human cells and melanoma cells. Biond's is a human trial, but with one patient reported and no efficacy data released.

The caution is stated plainly by the sources themselves. The UCLA findings remain preliminary, and Biond says the trial is designed to establish initial safety and tolerability while assessing early signals of clinical activity.

Next steps are already defined. Biond's dose-escalation trial continues across multiple clinical sites, with higher doses to follow the 0.3 mg/kg level. For navtemadlin, the open question is whether the lab results hold up in further research, including against solid tumors.