mRNA cancer vaccines pass major milestone

Hello Nature readers,
This week, we discover that an mRNA vaccine has passed a major milestone, learn that people who live extraordinarily long lives have more cancer-killing immune cells and hear that knocking out two genes can make T cells more aggressive against solid tumours.

mRNA vaccine holds cancer back

A personalised mRNA vaccine developed by Merck and Moderna has become the first to show success in a late-stage clinical trial. In an unpublished study of 1,100 people with advanced melanoma, an mRNA vaccine called intismeran reduced the chance of cancer recurrence when combined with the immunotherapy drug pembrolizumab, compared with immunotherapy alone. Each participant in the trial had their tumour sequenced to identify their unique mutated proteins or neoantigens. An mRNA vaccine was then made that instructs the body to make those neoantigens — priming the body to recognise the cancer as a threat.

Cancer-killing cells in those who live to 110

People who live to 110 years and older have large populations of a rare type of immune cell that can kill cancer. These killer T cells might help people to live to extraordinarily long ages by fighting off cancer — although this has yet to be proved. “Most of immune ageing research has focused on decline,” says biologist Kosuke Hashimoto, who co-authored the research. “Our study suggests that even at extreme old age, the immune system may still selectively adapt.”

CRISPR takes the brakes off T cells

Scientists looked at 20,000 genes and found two that, if snipped out using CRISPR, turn sluggish T cells into an army of millions that ignore multiple suppression signals to swarm and take out five types of cancer in mice. Removing the first gene, P2RY8, caused five to ten million T cells to infiltrate the solid tumours, a breakthrough that makes it easier to study these otherwise rare immune cells. “That completely changed what was possible,” says bioinformatician Qi Liu who co-authored the paper. Slicing out the second gene, GNAS, blocked the cancer’s immune suppression signals. “What we found is that many of those off switches run through one shared circuit, and disabling GNAS let the T cells stop listening to all of them at once,” says Liu.

Why cancer resists daraxonrasib

The development of mutant KRAS proteins drives resistance to a promising drug for pancreatic cancer. Researchers sequenced more than 800 genes in 44 people with pancreatic cancer before and after they underwent treatment with daraxonrasib. They found that more than half of participants had a reactivated RAS pathway signalling after treatment — a finding that could guide combination drug strategies.

The rush to freeze

With cancers on the rise in young people, the field of oncofertility has never been more important. But only around half of early-onset patients diagnosed from 2013 to 2021 spoke to their health-care practitioner about preserving their fertility. Others struggled to get an appointment with fertility clinics before their cancer treatment started. The expense can be a barrier too, with embryo freezing costing up to US$20,000.