Experimental cancer vaccine makes its own oxygen and gives T-cells a boost

by Katya Poltorak, Northeastern University

edited by Lisa Lock, reviewed by Robert Egan

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When it comes to priorities in life, oxygen tops the list. Humans can go weeks without food and days without water. Take away the ability to breathe, however, and the clock starts ticking within minutes as the brain begins shutting down. But the life-giving gas does even more heavy lifting than you might think.

The immune system, which battles cancer with the help of specialized fighters, such as T cells, relies on oxygen to mount its attack.

Now, Bouvé College of Health Sciences professor and director of the pharmaceutical and biomedical sciences graduate program Stephen Hatfield and his colleagues are enlisting oxygen in the cancer fight with a new vaccine designed to give T cells a powerful edge.

With recent chemical engineering Ph.D. graduate Alexandra Nukovic as first author, Hatfield's team recently published a paper in Cell Biomaterials describing the vaccine. It generates oxygen by triggering a chemical reaction at the injection site. It also sets up a training ground where T cells get a crash course in identifying enemy cells they can then target for destruction.

How tumors disarm immune cells

The vaccine's oxygen-generating feature addresses one of the major ways cancer weakens the body's defenses.

Most tumors contain regions where oxygen levels are very low. Known as hypoxia, this condition acts as a stealth weapon, sabotaging the immune system's attack before it even begins, Hatfield explained.

Low oxygen triggers the buildup of adenosine—the same chemical that signals sleepiness in the brain. In tumors, adenosine suppresses T cells, effectively putting them down for a nap right in the trenches.

"There are T cells in here that should be recognizing and destroying the tumor cells, but they're not doing it," Hatfield said, referring to the low-oxygen tumor environment that shuts down T cells.

Hypoxia can even cause defections within the immune system's ranks. Kristian Mark Jacobsen, co-founder of Danish biotech company Kripthonite Therapeutics, noted that in low-oxygen conditions, immune cells known as macrophages sometimes turn from cancer fighters into tumor protectors, shielding the enemy they would normally attack.

Moreover, despite being a promising treatment strategy, vaccines themselves are associated with hypoxia at injection sites. The flurry of cellular activity uses up oxygen, hampering the very immune response the vaccine is meant to trigger.

The new platform Hatfield and his colleagues developed counters this effect. By generating oxygen locally, it puts immune cells in their best fighting shape before they head for the tumor. Hypoxia still awaits them when they get there, but they're better equipped to take on the cancer cells.

A sponge-like vaccine platform

The vaccine consists of a cryogel—a soft material with a network of interconnected pores. "Cryo" means cold, and the name comes from the fact that it's formed at -20°C (-4°F), Nukovic explained.

"Once it's taken out and thawed, it's very sponge-like," she said.

The cryogel also has shape memory and can be compressed to squeeze through a syringe needle. It will then spring back into shape on the other side.

That means a prick is all it takes—no surgical implantation required, Nukovic explained.

From oxygen therapy to prevention

The effort to counter hypoxia with oxygen builds on a groundbreaking discovery Hatfield's team made more than a decade ago.

As they reported in Science Translational Medicine in 2015, simply breathing oxygen-enriched air reduced hypoxia at the tumor site and allowed T cells to put up a stronger fight.

"There was a lot of excitement about it," Hatfield recalled. Breathing more oxygen to fight cancer? It's easy to see the appeal. However, it turned out breathing alone couldn't alleviate hypoxia in cancers that oxygen-rich blood struggled to reach.

The new vaccine tackles the problem from a different angle. It sets the cells up for success from the get-go rather than trying to pump oxygen to the tumor itself.

But oxygen is only half of its strategy.

Training T cells for tumors

The network of pores in the cryogel also acts as a tiny training station with rooms for immune cells to enter. Inside, they come into contact with antigens—proteins that teach T cells to recognize and target cancer cells for destruction.

In mice with tumors grown from prostate cancer cells, the vaccine slowed tumor growth and extended survival from 47 to 76 days.

For Nan Zhang, a researcher at The Wistar Institute, a biomedical research center, this method represents a new way of approaching the cancer fight. Rather than treating a strong immune response as the end goal, it asks whether that response translates into a successful attack.

"A vaccine can teach T cells to recognize cancer, but those cells still need to reach the tumor and remain effective once they get there," he said. "An important part of the equation (is) not just teaching the immune system what to attack but creating conditions that allow it to succeed," he added.

Vaccines made from materials similar to the cryogel have already shown a good safety record, Hatfield said. Following the promising results in mice, his team is refining the vaccine with the goal of eventually testing it in humans.

Publication details

Alexandra Nukovic et al, Oxygen-generating cryogel vaccines help overcome tumor antigen tolerance and induce durable antitumor immunity in prostate cancer, Cell Biomaterials (2026). DOI: 10.1016/j.celbio.2026.100578

Journal information: Science Translational Medicine

Key medical concepts

HypoxiaT-Lymphocytes

Clinical categories

OncologyAllergy and immunology Provided by Northeastern University Who's behind this story?

Lisa Lock

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