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Cancer patient receives ‘landmark’ treatment in world-first

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A woman with advanced ovarian cancer has become the first patient globally to receive an experimental off-the-shelf cell therapy.

Tracy Tomlinson, 58, was given the experimental drug ZI-MA4-1 at the Christie NHS Foundation Trust in Manchester.

The treatment forms part of a clinical trial evaluating its use against several cancer types, including ovarian, lung, head and neck cancers and sarcomas.

The Christie is leading the trial, with a second site at the Royal Marsden in London. It involves patients with advanced cancers who may have few other treatment options.

Tomlinson, from Chadderton in Greater Manchester, has undergone surgery and multiple rounds of chemotherapy since she was diagnosed in 2020.

She said: “They’ve got rid of the cancer twice but then it came back about two and a half years ago, and we’ve never seemed to get rid of it since then.

“The chemotherapy has shrunk it but when treatment stops, it has come back.

“It is a lot to live with and there’s been ups and downs – there’s been elation, there’s been disappointment, and bits in between.

“But I try very, very hard to remain very positive. Every day that I wake up is a positive. You’ve got to have hope.”

ZI-MA4-1 combines two approaches to cancer treatment.

It uses natural killer cells, known as NK cells, which are specialist immune cells that identify and destroy abnormal cells.

T-cell receptors on the donor cells are also engineered to recognise and target tumours producing a protein called Mage-A4.

Mage-A4 is found in several types of cancer and is considered by experts to be a potential target for attacking abnormal cells.

Unlike personalised treatments, ZI-MA4-1 is designed as an off-the-shelf therapy using immune cells from donors.

The treatment is manufactured in advance rather than being made separately for each patient, with hundreds of doses potentially produced from one manufacturing batch.

Experts believe this approach could make advanced cell therapies available to more patients, more quickly and at a lower cost.

Tomlinson was diagnosed with ovarian cancer that had spread shortly before Christmas 2020 and began treatment immediately.

By summer 2021, scans showed no evidence of disease, but the cancer returned around a year later.

Despite further treatment and 48 chemotherapy infusions, the cancer continued to return.

The former Civil Service manager was diagnosed with stage 3C ovarian cancer, meaning cancer growths had spread into the peritoneum, the tissue lining the abdominal cavity.

She currently has a tumour between her liver and kidney, as well as smaller tumours elsewhere.

She said: “They’ve got rid of the cancer twice but then it came back about two and a half years ago, and we’ve never seemed to get rid of it since then.

“The chemotherapy has shrunk it but when treatment stops, it has come back.

“It is a lot to live with and there’s been ups and downs – there’s been elation, there’s been disappointment, and bits in between.

“But I try very, very hard to remain very positive. Every day that I wake up is a positive. You’ve got to have hope.”

Tomlinson said she had been target-driven during her working life and had set herself high standards.

“But you can’t control cancer,” she said. “What I can control is how I look at it, how I deal with it, and trying to eat healthily and taking the positives in everything.

“And I’ve learned to appreciate the smallest of things that we take for granted – and the people around you and what they mean to you.

“Also, the beauty of outside and the trees and the colour of the trees and the birds singing.

“We just go from A to B, don’t we? Busy, busy, busy. But we never slow down and take in the wonder of what’s around us.

“I often think, ‘I’m still here’, and that’s helped me think, ‘Why can’t I still be here in 10 years?’, ‘Why can’t I still be here in 15 years?’

“And I believe taking all the treatments offered to me is helping me kick that can a bit further down the road.

“I don’t want to go anywhere. I’ve still got a lot of things I want to do and things I want to achieve.”

Tomlinson said her husband Paul, whom she married in 2022, is her “rock”. She is also close to her son Harry, 28.

Last year, she was referred to the Christie’s early-phase clinical trials team for extensive screening and learned she was eligible for the Zima-101 clinical trial.

She said: “I decided almost straight away that I was going to go for it.

“Then afterwards you think, ‘Am I doing the right thing?’, because it is a little bit scary being the first person in the world to have the treatment.”

She has received three infusions of the therapy, with the option of a fourth depending on her scan results.

She said: “If it benefits me, absolutely fantastic. But if it benefits other people in the future, that’s important too.

“I don’t want to have gone through everything I’ve gone through for nothing. I want to feel like I have made a difference.”

Professor Fiona Thistlethwaite, consultant medical oncologist at the Christie, said: “While this is an early-stage study primarily focused on safety, it represents an exciting step forward in efforts to develop new treatment options for people like Tracy with advanced solid tumours.

“We hope the knowledge gained will help shape future cancer treatments and ultimately improve outcomes for patients.”

Dr Jon Lim, consultant medical oncologist in advanced immunotherapy and cell therapy at the Christie, told PA: “What’s very exciting about this is that these are essentially not kind of antibody-based, but living cells.

“These are live immune cells that are infused in hundreds of millions back to the patient, and the idea of this is that it is a little bit more targeted.

“The reason this is very interesting is because this is the first of its kind globally in this approach, where it’s taking donor immune cells, manipulating or engineering them, and putting them into the recipient.

“Tracy is essentially getting somebody else’s immune cells that have been engineered to ‘see’ her cancer.

“We’re very excited. This is a novel approach in the cell therapy space. We are also really showcasing what we can do in the UK.”

Namir Hassan, chief executive of Norwegian company Zelluna, which makes ZI-MA4-1, described Tomlinson’s first dose as a “landmark moment”.

He said: “It represents the moment when years of research moved beyond the laboratory and into the clinic, offering a new potential treatment option for patients facing advanced cancers with limited alternatives.”

Only around 15 per cent of women survive ovarian cancer for five years or more after diagnosis.

Dr Diana Hernandez, director of immune and advanced therapies at Anthony Nolan, said: “NK cells have huge potential as off-the-shelf therapies, and this trial takes us one step closer to a wider application of engineered NK cells in the targeted treatment of cancers.”

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Hormonal health

Man City launch female athlete health education platform

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Manchester City has launched a female athlete health platform covering menstrual, pelvic and breast health, as well as nutrition.

The Her City website is designed for the club’s women’s first-team players, coaches, support staff, academy players and parents.

Manchester City says the platform is the first of its kind in the Women’s Super League and was developed over two years.

The project was led by director of performance services Emma Deakin, physical performance scientist Rosie Anderson and PhD student and first-team nutritionist Sarah Malone.

It grew out of PhD research into menstrual, pelvic and breast health and nutrition, with the team seeking to turn that work into an online educational resource.

The website divides the four areas into separate sections and provides peer-reviewed information that the club says has been critically analysed by experts.

Content will continue to be reviewed and updated as further evidence emerges.

Resources include posters, visual explainers, audio materials and downloadable educational content, with information tailored to different groups including players and parents.

The platform aims to improve knowledge, develop critical analysis skills and strengthen communication within football and at home.

It also includes material to help users assess misinformation they encounter on social media or elsewhere.

A confidential contact form allows users to raise concerns or ask questions directly of experts at Manchester City.

Parents of academy players can also access the platform, with resources intended to help them support their children during a key phase of their development.

Manchester City said its longer-term aim is to make the platform available to all women working across City Football Group.

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Wellness

Study links small bowel microbiome differences to women’s health

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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.”

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Fertility

Weight loss surgery improves menstrual health and PMOS symptoms, study finds

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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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