New cancer vaccine foils tumour escape mutations in animal studies

3 minute read

Animal studies show that the vaccine can bypass cancer cell defences by preventing the shedding of a protein that triggers an immune response.

Animal studies indicate that a new type of cancer vaccine stops the development of tumours by preventing cancer cells from shedding proteins that trigger an immune response.

The vaccine was also effective in reducing metastatic spread, the researchers reported in Nature. Preliminary results of the studies in mouse and macaque monkey models indicate that the vaccine is safe and effective; human trials are now being planned, researchers said. 

The vaccine targets two proteins, known as MICA and MICB stress proteins, expressed by cancer cells when their DNA is damaged. These proteins are either not detectable or detectable only at low levels in healthy non-cancerous cells. 

When the immune system detects these proteins, it triggers a coordinated attack by the T-cell and natural killer (NK) cell populations. To avoid detection by the immune system, tumour cells tend to shed their MICA and MICB proteins. 

To prevent this, the vaccine triggers an antibody response, which increases the density of these proteins on the surface of the cancer cells. This mechanism of action works via prevention of what’s known as proteolytic shedding. In addition, these antibodies make tumour antigens more “visible” to T-cells, as well as boosting the cytotoxicity of natural killer cells.  

“This vaccine is a sophisticated complex of different components designed to elicit responses in both key arms of the immune response we know are needed to achieve tumour control; that is, T-cells and antibody responses,” said Professor Robert Ramsay, co-head of the gastrointestinal cancer program at the Peter Mac Institute in Melbourne. 

“The biology of MICA / MICB is really interesting as it serves to activate NK cells while tumour cells cleave it off their surface, serving as a decoy to subvert host immune attempts to recognise and eliminate the tumour.  

“Here, the added bonus is that the antibody response can be exploited against tumour cells that attempt to avoid immune attack. This is achieved by natural killer cells. Impressive thinking all round,” said Professor Ramsay, who was not involved in the study. 

In the first part of the study, researchers tested the vaccine in mice with melanoma and triple-negative breast cancer. Both cancers have a high risk of metastatic spread after the removal of the primary tumour. 

One month after removal of the primary tumour, the vaccinated mice had a much lower incidence of lung metastases than the control group. “This vaccine design enables protective immunity even against tumours with common escape mutations,” the researchers wrote. 

They also tested vaccine safety and immunogenicity in macaque monkeys. After vaccination, the monkeys were shown to develop anti-MICA and anti-MICB antibodies with no apparent clinical side effects and no changes detected on blood chemistry testing. 

Professor Ramsay said that while the vaccine showed high efficacy in the studies, the survival rates of animals in the studies varied. “The proof will be when this moves to the clinic and we see whether combining other immunotherapy strategies will achieve the tumour control we strive for.” 

Professor Ramsay said there had been a resurgence of interest in vaccines since covid.  

“Pharma and others have reinvigorated their attention to vaccines in the cancer space in part because of this, and also the other remarkable successes with immunotherapy checkpoint inhibitory antibodies,” said Professor Ramsay.  

“Indeed, the past disappointment with cancer vaccines is likely to be forgotten when vaccines are combined with checkpoint targeting therapies.” 

Nature 2022, online 25 May

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