Tracy Tomlinson, 58, from Chadderton in Greater Manchester, has become the first patient in the world to receive a pioneering new cancer therapy, ZI-MA4-1, at the Christie NHS Foundation Trust in Manchester as part of a clinical trial evaluating the treatment for several types of cancer.
The therapy is designed to treat ovarian cancer, lung cancer, sarcomas and head and neck cancer. The trial, led by the Christie, also has a site at the Royal Marsden in London. Many participants have few other survival options.
How ZI-MA4-1 works
The new therapy combines two powerful methods. It harnesses the body's natural killer (NK) cells, specialist immune cells that destroy abnormal cells, and uses engineered T-cell receptors (TCRs) to recognise and target tumours producing a protein called Mage-A4, found in several cancers.
Unlike personalised treatments, ZI-MA4-1 is an "off-the-shelf" therapy using donor immune cells, manufactured in advance from donor cells. Hundreds of doses can be produced from a single batch, potentially making advanced cell therapies available to more patients more quickly and at lower cost.
Tracy's journey
Mrs Tomlinson was diagnosed with advanced ovarian cancer (stage 3C) shortly before Christmas 2020. After surgery and several rounds of chemotherapy, scans showed no evidence of disease by summer 2021, but the cancer returned a year later. Despite further treatment and 48 chemotherapy infusions, the cancer kept coming back.
She currently has a tumour between the liver and kidney as well as small tumours elsewhere. She told the Press Association: “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.”
She added: “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.”
Decision to join trial
Last year, she was referred to the Christie’s early phase clinical trials team for extensive screening and learned she was a suitable candidate for the Zima-101 clinical trial. “I decided almost straight away that I was going to go for it,” she said. “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 had three infusions of the therapy, with the option of another depending on scan results. “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.”
Expert reactions
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 firm Zelluna, which makes ZI-MA4-1, described Mrs Tomlinson’s first dose as a “landmark moment”, adding: “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.”
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. At Anthony Nolan we have long seen the potential of cellular therapies like this to transform the lives of patients with blood cancer. Today’s research represents exciting progress for patients with solid tumours to benefit from these promising therapies.”
Only around 15% of women survive ovarian cancer for five years or more after diagnosis.
