New type of immunotherapy shows promising results

Disease and treatment 27. mar 2021 3 min PhD student Rosa Lundbye Allesøe Written by Kristian Sjøgren

Early-phase clinical trials testing personal neoantigen-directed vaccine are showing encouraging results. The immune system learned to recognize the cancer cells, and everyone who got vaccinated is still alive.

Researchers from Dana-Farber Cancer Institute, Brigham and Women’s Hospital and the Broad Institute of MIT and Harvard and others have developed a personalized cancer vaccine, NeoVax, and the early trial results are encouraging.

Four years ago, researchers showed that NeoVax induces an immune response against cancer, and now a new analysis of personal data shows that NeoVax causes a long-lasting immune response and remains effective in case of relapse.

The result is that all eight people who participated in the experimental cancer treatment trial are still alive, despite having a very aggressive type of late-stage cancer.

The research results have been published in Nature Medicine. Rosa Lundbye Allesøe from the Novo Nordisk Foundation Center for Protein Research carried out some of the data analysis.

“We found that the vaccine not only stimulates an immune response but that the immune system also stores this response as memory cells. This shows that the vaccine has a long-term effect. This is really good news for this interesting new type of immunotherapy,” says Rosa Lundbye Allesøe.

Vaccine boosts the immune system in differentiating between cancer cells and healthy cells

The researchers got the neoantigen-directed vaccine to work by taking DNA from both the healthy cells and cancer cells of a person with cancer and analysing the DNA to find mutations.

These differences result in different peptides being presented to the immune system on the surface of the cells. Healthy cells have one variant and cancer cells have another.

The researchers used this information to synthesize copies of the peptides present only in cancer cells but not in healthy cells.

In developing the personal vaccine, the researchers recreated the best candidates among all the cancer peptides they could find. They then inserted the peptides into a vaccine that contains components to induce an immune response and injected it into the trial participants.

“The immune system collects the peptides and uses them as a template to create an immune response and attack all cells that have these peptides. Since the peptides are only found in or on cancer cells but not healthy cells, the immune response will specifically target the tumours,” explains Rosa Lundbye Allesøe.

Immune system remembers cancer cells

The researchers included six people with late-stage and malignant melanoma when they published the first results of this experimental type of cancer treatment in 2017. The new study included two additional people.

The initial results showed that the participants developed an immune response to the cancer cells. Four participants did not experience cancer relapse after 25 months of follow-up, and two received additional treatment.

In the new study, Rosa Lundbye Allesøe processed the data on the development of individual immune cells before and after vaccination, and she and her colleagues showed that the immune system attacks the cancer cells immediately after vaccination and develops a long-lasting response.

To continue to attack specific targets in cancer cells without being constantly reminded by a vaccine, the immune system develops memory cells, which retain a fragment of the peptide to be attacked.

The new study shows that these memory cells became established and that the trial participants continued to have a response for an average of 4 years after treatment.

“We examined samples of all the cells of the participants’ immune system following the various vaccinations to determine how the immune response changed over time, and in the laboratory we can see how the immune cells bind specifically to the cancer cells and kill them,” says Rosa Lundbye Allesøe.

All eight participants still alive despite aggressive cancer

The result is also evident in the health of the participants. All eight are still alive despite having a deadly type of cancer.

Six have achieved a complete response, with doctors finding no evidence of cancer.

However, five participants have experienced relapse and one has undergone surgery to remove metastasis in the brain.

“Our data also show that the vaccine does not merely activate the response against the peptides that we have introduced but also has triggered epitope spreading, responding to peptides that were not included in the vaccine,” explains Rosa Lundbye Allesøe.

Should be combined with other types of immunotherapy

Rosa Lundbye Allesøe thinks that this new therapy has great potential and can become an important way to battle cancer.

However, she also thinks that it cannot stand alone but will instead become even more potent by combining it with other types of immunotherapy, such as immune checkpoint inhibitors, which remove the brakes from the immune system so that it responds much more strongly.

“The more ways we can attack cancer, the more difficulty the tumours have in avoiding the immune system. In particular, the results strongly indicate that personalized cancer vaccines in combination with immune checkpoint inhibitors may be effective in controlling metastasis,” concludes Rosa Lundbye Allesøe.

Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma” has been published in Nature Medicine. Rosa Lundbye Allesøe is a PhD student at the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen, which the Novo Nordisk Foundation supports.

I'm a PhD student at Novo Nordisk Foundation Center for Protein Research in the Rasmussen group and at the Copenhagen Research Centre for Mental Healt...

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