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Ovarian cancer vaccine project advances
A UK project to develop the world’s first ovarian cancer prevention vaccine is gathering pace.
A new study will see researchers funded by the charity Cancer Research UK initially establish the targets for the vaccine.
They will investigate which proteins on the surface of early-stage ovarian cancer cells are most strongly recognised by the immune system and how effectively the vaccine kills mini-models of ovarian cancer called organoids.
If this research is successful, work will then begin on clinical trials of the vaccine. The hope is that in the future, women could be offered this vaccine to prevent ovarian cancer in the first place.
There are around 7,500 new ovarian cancer cases every year in the UK, and it is the 6th most common cancer in women.
There is no current screening programme for the disease and some women with inherited copies of altered genes are at higher risk.
Ovarian cancer risk is up to 65% higher in women with altered BRCA1 genes, and up to 35% higher in women with altered BRCA2 genes, compared to women without these gene alterations.
Currently, women with BRCA1/2 alterations are recommended to have their ovaries removed by the age of 35, which means that they can’t have children in the future, and they experience early menopause.
Director of the Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine at the University of Oxford and lead for the OvarianVax project, Professor Ahmed Ahmed, said: “We need better strategies to prevent ovarian cancer. Currently women with BRCA1/2 mutations, who are at very high risk, are offered surgery which prevents cancer but robs them of the chance to have children afterwards. At the same time, many other cases of ovarian cancer aren’t picked up until they are in a much later stage.
“Teaching the immune system to recognise the very early signs of cancer is a tough challenge. But we now have highly sophisticated tools which give us real insights into how the immune system recognises ovarian cancer.
“OvarianVax could offer the solution to prevent cancer, firstly in women at high risk but also more widely if trials prove successful. Thanks to this funding, our research can take a big step forward towards a viable vaccine for ovarian cancer.”
Previous research by Professor Ahmed and his team at the University of Oxford has found that immune cells from ovarian cancer patients “remember” the tumour.
Building on this research, the scientists will train the immune system to recognise over 100 proteins on the surface of ovarian cancer, known as tumour-associated antigens.
They will find out which of these antigens trigger the immune system to recognise and kill cells which are becoming ovarian cancer.
Tissue samples from the ovaries and fallopian tubes of people with ovarian cancer will be used to recreate the early stages of ovarian cancer in the study.
The researchers will work with patient and public representatives to establish who would be willing to take the vaccine, who could benefit most from it, how it could be administered and how to ensure it is taken up by as many eligible women as possible, if it is successful in future clinical trials.
It will still take many years for the vaccine to reach a point where it is widely available to women at risk of ovarian cancer.
However, this funding is an exciting step towards a world where doctors can prevent ovarian cancer at an early stage, rather than treating it once the disease has already taken hold.
Chief executive of Cancer Research UK, Michelle Mitchell, said: “Projects like OvarianVax are a really important step forward into an exciting future, where cancer is much more preventable. This funding will power crucial discoveries in the lab which will realise our ambitions to improve ovarian cancer survival.
“OvarianVax builds on the exciting developments in vaccine technology during the pandemic. This is one of many projects which we hope will give women longer, better lives, free from the fear of cancer.”
Small bowel microbiome differences between women and men may help explain why some conditions are more common in women, a study suggests.
The small bowel microbiome is the community of microorganisms living in this part of the digestive tract, where they play vital roles in immune function, metabolism and hormonal regulation.
Researchers found differences between women and men in the composition and organisation of these microbial communities. One bacterial community containing Granulicatella was found only in women.
The study was conducted by investigators at Cedars-Sinai Health Sciences University.
Ruchi Mathur, director of clinical research and clinical operations for the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai and corresponding author of the study, said: “One intriguing finding was a bacterial community containing Granulicatella, which we found only in women.
“Bacteria in this community appear at increased levels in women with polyendocrine metabolic ovarian syndrome, formerly known as polycystic ovary syndrome.”
The researchers also identified differences between women and men in how microbes in the small bowel produce fructans, complex carbohydrates known to trigger digestive symptoms in irritable bowel syndrome (IBS).
IBS is far more common in women than men.
Mathur, who is also a professor of medicine, said: “Our findings show that biological sex is a critical variable in the small bowel microbiome.
“We must consider it as we move toward more personalised approaches to understanding and treating disease.”
An experimental cancer drug reduced bone loss and body fat in mice modelling post-menopausal changes, early research suggests.
The compound, CADD522, appeared to strengthen bones and help the animals stay leaner after surgery designed to mimic hormonal changes seen after menopause.
The treatment remains at an early experimental stage and has so far only been tested in animals.
The study, led by the University of East Anglia, investigated CADD522, which was originally developed to block a protein involved in the growth and spread of several cancers.
Mice treated with the compound for eight weeks showed significant improvements in bone health. Scans found increased bone volume and better preservation of the honeycomb-like structures inside bones that are crucial for strength and resilience.
Blood tests suggested the treatment stimulated new bone growth without interfering with the body’s normal process of breaking down and rebuilding bone.
Dr Darrell Green, lead researcher from UEA’s Norwich Medical School, said: “Osteoporosis affects around one in three women over the age of 50, leaving sufferers vulnerable to painful fractures that can seriously impact quality of life.
“Current treatments exist, but many are plagued by side effects, safety concerns or inconvenient dosing schedules that make long-term use difficult.”
The researchers also found that mice receiving CADD522 weighed less than untreated mice despite eating the same amount of food.
They had less body fat and fewer fat deposits in their bone marrow, a process commonly seen after menopause and linked to declining bone health.
The team also examined brain tissue and found that the drug appeared to reverse several menopause-related changes in fatty acids.
Levels of omega-3 fats including DHA remained largely intact, while several other lipid abnormalities shifted back towards healthier patterns.
Green said: “We didn’t directly test for memory or thinking ability, but our work raises questions about whether this drug could one day help address wider menopause-related health problems.”
Safety experiments in mice, rats and dogs found that CADD522 could be taken orally and was well tolerated.
The compound also appeared to be metabolised more slowly in human tissue than in rodents, potentially improving its performance in people.
“This is still in the early stages and has so far only been tested in animals but we hope that the benefits will translate to humans to ultimately reduce fracture rates,” added Green.
The research was led by UEA in collaboration with the University of Maryland, the Scintillon Research Institute in San Diego and the University of Stirling.
Safety testing was funded by The Sir William Coxen Trust as part of the development of CADD522 as a childhood cancer treatment.
Weight loss surgery was linked to more regular periods and fewer polyendocrine metabolic ovarian syndrome (PMOS) symptoms in women aged 18 to 45 living with obesity in a recent study.
The researchers recommend that women undergoing the procedure have access to preconception care and reproductive counselling to support their reproductive health.
Researchers at the University of Surrey analysed data over 24 months from 84 women who underwent bariatric surgery and 18 women living with obesity who did not have surgery.
Of those who underwent surgery, 49 had gastric bypass procedures and 35 had gastric sleeve surgery.
Women who underwent metabolic bariatric surgery lost more than 30kg on average at 12 and 24 months after the procedure.
Among women with polycystic ovaries, the condition persisted in only 10 per cent after 24 months.
Women also reported a resolution of clinical hirsutism, or excess body hair, by 12 months.
Women who had previously experienced irregular periods reported more regular menstrual cycles after surgery.
Professor Martin Whyte, co-author of the study and professor of metabolic medicine at the University of Surrey, said: “A large proportion of those undergoing bariatric surgery are women of reproductive age, who may be planning a pregnancy in the coming years.
“So much remains unknown about the impact of this type of surgery on women who are planning to have children.
“This raises the question of when the ideal time after surgery is to conceive.”
Women have a higher prevalence of obesity than men, with 57 per cent of women in the UK classified as overweight and 27 per cent living with obesity, which can affect fertility and the health of an unborn baby.
The researchers said 17 women had healthy pregnancies following surgery.
Although this was not specifically examined in the study, no difference in birth weight was observed between babies conceived within or after the first year.
Dr Kathryn Hart, co-author of the study and associate professor in nutrition and dietetics at the University of Surrey, said: “What we have found is that bariatric surgery positively affects the reproductive health of women living with obesity and can improve the likelihood of them having a healthy pregnancy after surgery.
“Dysregulated hormone levels, irregular periods and conditions such as polycystic ovaries are affected by obesity.
“By reducing this, what we have seen is that it can lead to improvements without the need for medication.
“We would suggest that clinicians consider medical intervention for obesity to treat irregularities in the menstrual cycle and issues with fertility.”
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