Centenarians, babies and cancer vaccines...
This week, Professor Stebbing highlights a landmark trial for a personalised cancer vaccine, fresh insights into lifelong immune protection, and how genetic screening at birth could identify cancer risk earlier.
A personalised mRNA vaccine for melanoma reaches a major milestone
Merck and Moderna have announced that their personalised mRNA cancer vaccine, known as intismeran, has significantly reduced the risk of melanoma returning in a large phase III clinical trial - the most rigorous kind of study in medicine. This is the first time an mRNA-based cancer treatment has succeeded at this late stage of testing, and it marks a significant step forward from decades of research into cancer vaccines.
The trial (INTerpath-001) enrolled 1,137 patients with high-risk melanoma whose tumours had already been completely removed by surgery. Patients received either pembrolizumab alone (a well-established immunotherapy drug already used as standard treatment) or pembrolizumab together with the personalised vaccine. After five years of follow-up, the combination reduced the risk of the cancer recurring or causing death by 49% compared with pembrolizumab alone (hazard ratio 0.51). It also reduced the risk of the cancer spreading to distant parts of the body by 59% (hazard ratio 0.41).
These are substantial results. Overall survival data are not yet mature. What makes this approach so remarkable is how the vaccine is made. Each patient's tumour is genetically sequenced to identify the specific mutations unique to their cancer. Algorithms then predict which of the resulting abnormal proteins, called neoantigens, are most likely to be recognised and attacked by that individual's immune system. An mRNA construct encoding up to 34 of these neoantigens is then manufactured specifically for that patient: effectively a molecular photograph showing the immune system exactly what it should be targeting. Pembrolizumab works by removing one of the brakes that cancers use to suppress immune responses.
The vaccine and the drug therefore work as a team: one teaches the immune system what to recognise, and the other helps sustain the attack. Perhaps most encouraging is what this trial may mean for other cancers. Personalised vaccines are already being investigated in pancreatic cancer, bowel cancer, stomach cancer, lung cancer and triple-negative breast cancer.
Crossing this phase III threshold is genuinely significant, and the companies have said they plan to engage with regulatory authorities about a filing for approval.
Read more: Merck press release - INTerpath-001 trial | STAT News coverage
How the immune systems of people who live past 100 may hold clues about cancer protection
A new study published in the journal Cell Reports has found that people who live beyond 110 years - known as supercentenarians - tend to have unusually high numbers of a rare type of immune cell called CD4 cytotoxic T lymphocytes (CD4 CTLs). These cells, which appear to have expanded specifically in response to threats encountered over a lifetime, may offer a glimpse into one of the biological secrets of extreme longevity, with intriguing implications for cancer. Most of us know CD4 cells as the 'helper' cells of the immune system, responsible for coordinating immune responses.
What makes the CD4 CTLs found in supercentenarians unusual is that they have acquired the ability to directly kill other cells. The study found that the proportion of these cells increased steadily with age: around 4% in people aged 70-99, rising to 9.6% in centenarians (100-109), and reaching 17.6% in supercentenarians (110 and older). Crucially, the cells showed signs of having expanded in response to specific targets, forming large, active clones without the signs of exhaustion you might expect in very old immune cells, meaning they were actively doing something rather than simply accumulating passively.
When researchers examined the 'barcodes' of these T cells, they found matches with immune cells previously identified in patients with non-small cell lung cancer, breast cancer, and liver cancer, raising the possibility that these cells may be targeting cancer-associated antigens. Cancer risk rises sharply with age because cells accumulate more mutations over time, while the immune systems that normally patrol for abnormal cells may become less effective. Supercentenarians may have retained an unusually capable cellular surveillance system that continues identifying and eliminating threats, including potential cancers, decade after decade. Important caveats apply.
It is not yet established whether these unusual immune cells help people reach extreme old age, or whether they are simply a feature of having survived so long. Correlation is not causation, and this research needs significant further investigation before any clinical application could be considered. But the findings add to a growing body of evidence that the immune system's relationship with cancer is central to healthy ageing.
Read more: Cell Reports - original study | ScienceAlert coverage
Genomic newborn screening: catching cancer-predisposition genes from birth
A series of new studies is beginning to demonstrate what becomes possible when whole-genome sequencing moves from the genetics clinic into routine newborn screening. One Belgian programme (BabyDetect) screened 3,847 babies for 165 treatable conditions; an Australian study (BabyScreen+) examined 605 genes in 1,000 newborns. Both found meaningful numbers of serious, actionable diagnoses that standard heel-prick testing would have missed.
A separate study published in Nature Communications in August 2026 focused specifically on cancer: using a panel of 11 genes linked to paediatric cancer-predisposition syndromes, researchers found pathogenic variants in nearly 7% of the children screened. Among the conditions these programmes can detect are inherited genetic variants that significantly raise the risk of developing certain cancers later in life. Identifying these at birth opens the possibility of lifelong surveillance, earlier intervention and, in some cases, preventive treatment during the window when action is most effective.
Researchers are also wrestling carefully with the question of what to report and when: a variant that only becomes relevant in adolescence or adulthood raises different ethical questions than one requiring immediate action in a newborn. The wider programme raises important questions about consent, equity and the capacity of health systems to act on what they find. But the direction of travel is clear: as sequencing becomes cheaper and our understanding of treatable genetic conditions grows, it is increasingly possible to see a future where a single test at birth provides a lifelong genetic roadmap, used carefully and selectively to act at the moments when early knowledge makes the greatest difference.
Read more: BabyScreen+ study - Nature Medicine | Medical Xpress coverage
As always, if anything in this week's update feels relevant to your own situation or that of someone you care for, please speak with your clinical team before making any decisions. Research findings, even encouraging ones, take time to translate into treatment guidelines.
With thanks to Professor Justin Stebbing for his insights and research.