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Excited mice herald a new method for more effective cancer vaccines
The tumours disappeared in mice. We can't say for sure if this will work in humans, but it looks really promising, researcher says.
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Norwegian researchers have developed a method to make cancer vaccines more effective.
By adding a light-sensitive substance to a cancer vaccine and shining a lamp from the outside, the vaccine protein is released at the right place in the cell.
Combined with a substance that mimics RNA from viruses, this gives a hefty boost to the immune system.
The researchers have tested the method on mice with cancer.
They observed that the tumours in the mice disappeared. The response from the immune system's T cells was also 100 times stronger than if they had just used the cancer vaccine alone.
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The results have now been published in the journal npj | Vaccines.
Vaccines as a treatment for cancer
Vaccinating against the HPV virus has prevented cervical cancer with great success.
Researchers are also trying to develop vaccines against cancers that have already been detected. These vaccines are a form of immunotherapy called therapeutic cancer vaccines.
This vaccine type is designed to teach the immune system to detect a characteristic or "antigen" on the outside of cancer cells that triggers a defence response.
The characteristic may be common to several types of cancer or unique to the tumour in the individual patient.
A peptide or protein found on the cancer cells, or their genetic recipe, is added to the cancer vaccine.
The goal is for the immune system to learn to recognize the cancer cells, and for killer T cells to attack them.
Current vaccines not effective enough
“Cancer cells develop mutations and produce antigens that are specific to them, which the immune system can target,” says Pål Kristian Selbo, who collaborated with Anders Høgset to lead the new study.
“The problem is that cancer tumours can suppress the immune response, which makes it more difficult to establish effective T cell responses.”
The researchers looked at peptide- or protein-based vaccines in the new study.
This type of vaccine is in clinical trials, but has so far had only limited success and is not yet being used in regular cancer treatment.
“The problem is that the vaccines are not very effective,” Selbo says.
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He is a senior researcher and group leader at the Department of Radiation Biology in the Institute for Cancer Research at the Norwegian Radiumhospitalet and Oslo University Hospital.
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Activating killer cells is key
The peptide or protein is taken up by "antigen-presenting cells" that are part of the immune system. These are cells that process and display antigens for T cells.
The protein is brought into the cell in a process called endocytosis. This means that the outer cell membrane folds inward and creates a small bubble, or vesicle, that encapsulates the protein in an endosome.
The vesicle contains enzymes to break down the protein.
“This has been called the cell's garbage system since ancient times,” says Selbo.
“When the peptides and proteins are broken down, a signal is normally sent from the antigen-presenting cells to the T cells.”
When the breakdown goes too far, Selbo explains, the antigen is presented mainly to what are called helper T cells. But effective cancer control often requires strong activation of killer T cells.
Protein released with light
The researchers needed to prevent the vaccine protein from being broken down too much.
“We have to release them from the endosomes,” says Selbo.
This is where the light technique comes in.
The method that Norwegian researchers have developed over several years is an intracellular, light-controlled drug delivery method called photochemical internalization (PCI).
It is based on the patient, or in this case a mouse, ingesting a light-sensitive substance simultaneously with the vaccine protein.
“The light-responsive substance attaches itself to the membrane of the vesicles. When we shine the light on them, the photons hit the photosensitive substance.”
The researchers shine a blue light lamp on the mouse. A red light is used to penetrate deeper into the tissue via laser.
The photosensitive substance absorbs light at specific wavelengths and gains greater energy, forming toxic oxygen compounds. This destroys the membrane of the endosomes, and the protein or peptide can escape freely into the cell.
“This mechanism processes the antigen and prepares it for presentation to killer T cells,” says Selbo.
The alarm is activated
This method induces a stronger reaction from the right T cells. Researchers have demonstrated this previously.
The new part of the process is that the researchers combine the method with an adjuvant, a special substance that speeds up the immune system into overdrive.
“The combination of the three components is the key finding of the study,” says Selbo.
The substance they have used as an adjuvant is synthetic RNA, which resembles the genetic material from viruses. This sets off an alarm in the body.
The RNA used by the researchers is special because it consists of double-stranded RNA, which the immune system perceives as a signal of viral infection. Unlike most of the body's own RNA, this molecule consists of two strands.
“This sends a danger signal to the immune system that causes it to attract even more immune cells than when using the methods separately,” Selbo says.
Holds promise for use against several types of cancer
Selbo notes that the combination presented in the new study has not yet been tested on people with cancer.
“That is one of the limitations. We can’t say for sure whether this will work in humans, but it seems very promising in a preclinical model,” he says.
Although the new combination treatment has so far only been tested in mice, parts of the technology have crossed over to humans. A clinical study has been conducted in healthy volunteers, which showed that the method could be used safely.
PCI has also previously been tested in several clinical cancer treatment studies. A Norwegian company called PCI Biotech was actually formed based on using the light-induced method, but it has now ceased operation.
In the new mouse study, the treatment was tested against HPV-related cancer, but Selbo says that the PCI method holds potential for treating several forms of cancer.
In addition to the HPV antigen, the researchers also obtained enhanced immune responses against other antigens, including telomerase and hepatitis B virus.
In the future, this method may also be included in personalized cancer vaccines, which are tailored to the characteristics of the tumour in the individual patient, says Selbo.
The research has been supported for many years by the Research Council of Norway, as well as Radforsk and the South-Eastern Norway Regional Health Authority.
Hoping to see further development
Markus Haug is a researcher and immunologist at NTNU’s Department of Clinical and Molecular Medicine.
He researched the PCI method a few years ago and has collaborated with Pål Kristian Selbo, among others. But he has not followed up in recent years and has not been involved in the new study.
Haug says it is exciting to see what researchers have developed since his involvement.
The findings are not entirely unexpected, says Haug.
“Increased T-cell response to vaccination with PCI has been shown before. This study shows a clear additional effect when PCI vaccination is combined with an adjuvant and also demonstrates that the effect can be achieved with different types of vaccines.”
What is significant is that all the treatment components tested in the new study – the PCI method, the adjuvant and the vaccine – have been tested separately on humans. This brings us closer to being able to test the new method in humans,” says Haug.
He also says that the anti-tumour effect in mice was strong. He was impressed himself when he previously tested PCI as a strategy to increase the effect of cancer vaccines in mice.
“I thought it was absolutely incredible. I’ve rarely been involved in a project where things worked so well.”
He does not think the method will be suitable for increasing the effect of regular vaccines right away, due to the risk of side effects, but he does believe it will be suitable as a cancer treatment.
“I still think it is a very exciting method and I’d like to see someone develop the whole thing further.”
Reference:
Pål Kristian Selbo et.al.: Photochemical internalization enhances in vivo immunity to peptide‑ and protein‑based vaccines with synthetic dsRNA adjuvants. npj Vaccines, 2026. Doi.org/10.1038/s41541-026-01554-1
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Translated by Ingrid P. Nuse
Read the Norwegian version of this article at forskning.no
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