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Cancer vaccine and adoptive T-cell therapy could benefit patients with advanced ovarian cancer- study

Combining a personalised vaccine with T-cell therapy yielded control of ovarian cancer within three months, scientists have shown

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Combining adoptive T-cell therapy (ACT) with a personalised cancer vaccine could benefit patients with late-stage, drug-resistant ovarian cancer, a Ludwig Cancer Research study has shown.

Researchers led by Ludwig Lausanne’s Sara Bobisse, Alexandre Harari, Lana Kandalaft and director George Coukos analysed responses to the combination therapy of 18 patients with advanced ovarian cancer who had previously participated in a clinical trial evaluating a therapeutic regimen that incorporated the personalised cancer vaccine.

In the current study, patients received an infusion of their own vaccine-primed, circulating immune cells (specifically, T-cells), followed by multiple periodic doses of their personalised vaccines.

The researchers reported that combining the personalised cancer vaccine with T-cell therapy, a type of immunotherapy that makes a patient’s immune cells fight cancer, yielded control of the disease within three months in 12 of 17 patients.

The treatment was also found to be safe and relatively well tolerated.

“This treatment could not eliminate tumours, but it did provide considerable benefit to many of the patients, who had all undergone extensive treatment prior to enrolling in the trial and were in the late stages of the disease,” said Kandalaft.

Ovarian cancer is the sixth most common cancer in the UK, with around 7,500 new cases every year.

Like many other malignancies, ovarian cancer has so far proved largely resistant to immunotherapies, most of which harness killer T-cells, which destroy sick and infected cells.

Ovarian cancer cells do, however, express neoantigens, which are randomly mutated proteins that can activate anti-tumour T-cell responses.

Multiple approaches are today being developed at Ludwig Lausanne and elsewhere to target neoantigens for cancer immunotherapy. The personalised dendritic cell vaccine, developed over the past dozen years under the leadership of Kandalaft and Coukos, is one of them.

To make the vaccine, researchers first coax precursor immune cells isolated from patients to turn into dendritic cells, which present cancer antigens to killer T-cells to direct and activate their anti-tumour responses.

These dendritic cells are then expanded in culture and pulsed with an extract of cancer cells from a patient’s tumour that is chemically treated to improve uptake and processing of antigens by the cultured immune cells.

The vaccine is then injected into its corresponding patient’s lymph nodes, the anatomical site where dendritic cells activate anti-tumour T-cells.

In the current study, patients received chemotherapy followed by ACT using vaccine-primed T-cells that were expanded in culture in the presence of stimulatory immune factors. The ACT was followed by several cycles of vaccination.

“We were very happy that we could demonstrate how the combination therapy improved anti-tumour immune responses, and that those changes correlated to patient benefit,” said Ludwig Lausanne’s Bobisse.

“Most notably, we could show that T-cells targeting the neoantigens were reinvigorated by the combination therapy and correlated with positive responses to the therapy.”

Further, DNA sequences encoding neoantigens targeted by the T-cells were found at higher levels in circulating tumour DNA, suggesting they had invited the destruction of tumour cells.

Coukos, the director of the University Hospital of Lausanne Switzerland’s department of oncology, said: “This study illustrates how rational approaches to the design of immunotherapies can help overcome the barriers to immune responses that are erected by a variety of cancers, not least ovarian cancer.

“It has also taught us valuable lessons that we will be sure to apply to improve the efficacy of personalised cancer immunotherapies we’re developing here at Ludwig Lausanne.”

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Cultural stigma is a barrier to menopause help, black women say

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Cultural stigma and a lack of education are making it harder to get menopause help, ethnic minority women in Jersey have said.

The women came together to share their stories at an event in St Helier hosted by Eve Studios and Liberty Underwear.

Participants were encouraged to speak openly about the symptoms they had experienced.

Angela Mowanga, from Jersey, told ITV Channel: “I became dismissive about signs and symptoms. From our parents and our grandparents, they just carried on.

“I hardly heard the word menopause spoken about in my household. We never had things like hot flushes, itchy skin and tiredness.

“So for us to start talking about menopause, there is a taboo around it. A taboo that comes from ignorance but also not being willing to educate ourselves.

“We as women of colour, societies of colour, we have a lot of taboo subjects, which now have to be highlighted with the generation today.

“However, with the modern day, society is changing. And we hope programmes like this can actually be well received.”

Daisy Ayebale, from Jersey, added: “I think it’s important we are listened to. We need the right information from the experts, but we have also been overlooked when it comes to the healthcare system.

“We need to know this information before it’s too late, before you’re gambling with your health. We are glad to be changing the narrative, we are glad to be changing things right now. We are very hopeful.”

Research shows that black women are more likely to experience menopausal symptoms earlier, more intensely and for longer.

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Entrepreneur

TidalSense raises £14m to expand five-minute COPD test across NHS

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Cambridge health tech company TidalSense has secured £14.2m in funding led by Cross-Border Impact Ventures to expand its AI-powered lung disease test across the NHS and into Europe and the US.

The investment, which also includes returning backers BGF, Airstream Capital and Foresight Group, will fund the rollout of a handheld diagnostic device that can detect chronic obstructive pulmonary disease (COPD) in as little as five minutes.

It will also support the development of software to diagnose asthma using the same platform.

Donna Parr is managing partner at Cross-Border Impact Ventures.

She said: We look for technology that doesn’t just have a compelling story, but a body of clinical evidence behind it.

“TidalSense has both, with a CEO who has lived the problem she’s solving, and a product that’s already live within the NHS healthcare environment, saving time for patients who have waited years for an answer.

“It is also technology that can improve access to appropriate treatment for COPD sufferers on a global basis and especially for women who are often misdiagnosed.

“This is exactly the kind of impact we want to make with our investments.”

COPD, a progressive condition that restricts airflow and makes breathing increasingly difficult, is the third leading cause of death in England, according to the NHS.

It is responsible for about 30,000 deaths each year and costs the health service an estimated £1.9bn annually.

The company believes its technology could transform how respiratory disease is diagnosed by replacing the need for conventional spirometry in many settings.

Patients simply breathe normally into the handheld device for 75 seconds while artificial intelligence analyses the breath in real time.

A diagnosis is then displayed on screen, allowing clinicians to complete the entire process in around five minutes.

TidalSense says the technology allows clinicians to assess as many as six patients an hour, compared with roughly one an hour using spirometry, which has remained the standard diagnostic test for COPD despite changing little since it was first developed in the 19th century.

Spirometry requires patients to perform forceful breathing manoeuvres and typically needs specialist staff to administer.

TidalSense chief executive Ameera Patel said: “Our ambition is really bold and broad, and it is to have a really significant impact at a population level on chronic respiratory diseases like COPD and asthma.

“We want the test to be available to anyone the first time they present with symptoms, so there’s no bias in accessibility based on where you live, your socio-economic status or your ethnicity.”

Founded in 2013 by chief engineering officer Julian Carter, who holds a PhD in microelectronics and has more than 35 years’ experience developing medical devices, TidalSense has spent more than a decade building the technology.

Its AI models have been trained on more than 2.5 million recorded breaths to identify the distinctive patterns associated with COPD.

The device was introduced into the NHS last year and is now being used by public health providers in Suffolk, north-east Essex, Wales, Glasgow and community lung screening clinics across the south of England.

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Pregnancy

Women should not be pressured into an ‘ideal birth’, says health secretary

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Women should not feel pressured into an “ideal birth”, health secretary Yvette Cooper has said as she promised major maternity reform.

Cooper has returned to the Department of Health and Social Care 27 years after serving as public health minister under Tony Blair.

She said maternity and child health would be a major focus of her new role, alongside significant reforms to social care.

In an interview with the Guardian, Cooper said the changes should address any pressure on women to pursue a particular birth experience.

Families affected by maternity failures have repeatedly raised concerns that some units were reluctant to escalate medical interventions because of a preference for more natural births.

Cooper said: “I would worry about any mum feeling pressurised that there is somehow a kind of an ideal birth experience to live up to when it’s always different in every case, and you have to follow the evidence, you have to have informed choice.”

As one of her first actions as health secretary, Cooper said she intended to reintroduce binding national maternity standards.

The standards were dismantled during early Conservative NHS reforms and replaced with fragmented arrangements managed separately by individual hospital trusts.

A new maternity taskforce will draft the standards, which will have five central aims.

These include ending regional differences in levels of care and tackling racial inequalities linked to poorer outcomes in deprived areas, particularly for Black and Asian women.

Patient experiences will also form part of how standards are measured, while new targets will aim to identify underperformance before a major scandal develops.

Cooper, who became the first minister to take maternity leave while serving as a junior health minister in the early 2000s, said reports into maternity scandals had been “traumatic” to read and showed that systemic change was needed.

She said: “We’ve always said the NHS is about the cradle to the grave. I want to make it a personal crusade to put the cradle back at the heart of the NHS, and to have much more focus around maternity and child health, the very beginning of a family’s life, making that much more central to the priorities of the NHS, giving it the priority that it really deserves.”

Cooper said discussions about how maternity services could better listen to mothers’ needs had been taking place for the past two decades.

However, she said the emphasis on placing women and families at the centre of care appeared to have been lost.

She said: “It feels incomprehensible that we could be in this situation in the 2020s. I went back to look at some of the things that we’d done 25 years ago.

“And what did strike me was how much we were talking then about women and families being at the centre of care and about listening to women’s views.

“It is really shocking and distressing feeling that has somehow been lost in some of the maternity units where actually it should be the central issue.

“I had a direct interest. I was pregnant at the time. But I am really struck by it now, just feeling like there is this big gap in the priorities that the NHS has been focused on.”

Cooper said she was determined to provide a robust response to Donna Ockenden’s investigations into maternity failures at Shrewsbury and Telford and Nottingham, alongside Baroness Valerie Amos’s national investigation into England’s maternity system.

The investigations highlighted systemic clinical errors, understaffing and toxic institutional cultures. They found that hundreds of infant and maternal deaths were directly linked to failures to listen to mothers and defensive attempts to protect institutions.

Amos’s review faced criticism, including the resignation of an expert adviser over the lack of explicit warnings about “normal birth ideology”.

Families also questioned whether the review’s proposed statutory maternity commissioner would have sufficient independence.

Cooper said she remained committed to introducing the role.

She said: “In the end, the most important people in the maternity services are the mothers, babies, the families. But the point of having a maternity commissioner is to make sure that those issues are championed as part of an NHS.”

She also said reforms needed to address an oppositional culture between doctors and midwives in some trusts over when medical intervention during birth may be necessary.

Cooper said: “The thing that struck me most was the sense of women feeling they weren’t being listened to … And I think that probably does go back to issues around culture.”

Cooper, who served as foreign secretary until recently, said she was prepared for a difficult period in the health role as she sought to implement Andy Burnham’s social care reforms.

She said she remained committed to establishing the national care service announced by the prime minister the previous week.

A longstanding ally of former prime minister Keir Starmer and a former rival of Burnham in the 2015 Labour leadership contest, Cooper said she believed the change of prime minister had been necessary.

She said: “Of course it’s not easy. I really did not think it was possible to win the election when I came back into the shadow cabinet in 2022. It’s only because of what Keir did that we managed to win.

“But we had very difficult local election results … we have to respond to that. But I think we’ve got a sense of energy now.

“All of the things that Andy wants to focus on and drive are also just very much the things that that people are concerned about across the country.”

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