Researchers have achieved a world first, delivering an innovative cell therapy to a patient suffering from advanced ovarian cancer, based on modified immune cells from donors that precisely attack the tumor.
Patient Tracey Tomlinson, 58, from Chadderton in Greater Manchester, became the first person in the world to receive the experimental drug ZI-MA4-1, as part of an ambitious clinical trial called Zima-101, conducted in collaboration between the Christie Centre and the Royal Marsden Hospital in London, in an event described by experts as a "watershed moment" in the fight against malignant tumors.
Tracy's journey with the disease was not easy. Since being diagnosed with stage 3C ovarian cancer in 2020, she underwent immediate surgery and received 48 rounds of chemotherapy. Although the cancer disappeared twice during these years, it returned about two and a half years ago and settled as a major tumor between the liver and kidney, along with smaller tumors in various locations.
“They got rid of the cancer twice, but it came back,” Tracy, a former civil servant manager, told the Press Association. “Chemotherapy shrinks it, but it comes back as soon as it stops. It’s a life of ups and downs, but I try hard to stay positive. Every day I wake up is a victory, and we must hold on to hope.”
The innovation in this treatment lies in combining two effective immunological strategies
It relies on natural killer (NK) cells, which are specialized immune cells generated in the body to destroy abnormal cells, and are the first line of defense against tumors.
Second : The cells taken from the donors are engineered to be equipped with T-cell receptors (TCRs) that enable them to accurately recognize a protein called Mage-A4, which is produced by many cancer cells – including ovarian, lung, sarcoma, and head and neck cancers – making them able to target the tumor without harming healthy cells.
The key difference from traditional personalized therapies is that ZI-MA4-1 is an "off-the-shelf" treatment, meaning it is pre-made from donor cells, not individually for each patient. Hundreds of doses can be produced in a single manufacturing batch, potentially making it available to a larger number of patients more quickly and at a lower cost.
Dr. John Lim, consultant in advanced immunotherapy and cellular therapy at Christie, explains: "What's really exciting is that these aren't our antibodies, but living cells. Hundreds of millions of modified immune cells are injected into the patient's body, and their engineering makes them capable of 'seeing' cancer."
When Tracy was offered the opportunity to participate in the Zima-101 trial after a series of intensive tests, she didn't hesitate much. She said, "I decided to take the trial immediately, even though I felt a little scared being the first in the world. But I thought: if this treatment benefits me, that's great, and if it benefits others in the future, that's just as important. I don't want everything I've been through to be in vain."
Tracy has received three rounds of treatment so far, and may receive a fourth based on the results of upcoming tests.
Experts have praised the move, while emphasizing that the study is still in its early stages. Dr. Fiona Thistlewit, a consultant oncologist at Christie Hospital, said: "This is a preliminary study that focuses primarily on assessing safety, but it represents an exciting step in our efforts to develop new treatment options for patients with advanced solid tumors, and we hope that the knowledge gained will contribute to improving patient outcomes in the future."
For his part, Nemir Hassan, CEO of the Norwegian company Zelluna, which produces the drug, described Tracy's first dose as "a watershed moment in which years of research move from the laboratory to the clinic, to offer a new option for patients who have run out of options."
Dr. Diana Hernandez, Director of Immunotherapy and Advanced Therapies at the Anthony Nolan Foundation, commented: "NK cells have tremendous potential as off-the-shelf therapies, and this trial brings us one step closer to a wider application of this technology in the treatment of solid tumors, after it has proven effective in blood cancers."
The trial is taking place at a time when the five-year survival rate for women with ovarian cancer is only 15%, making any progress in this area a real glimmer of hope. The study includes patients with multiple types of cancer, including lung cancer, sarcoma, and head and neck cancer.
