Researchers have developed a modified CAR T-cell therapy that completely eliminated large solid prostate tumours in mice, offering hope for treating solid cancers in humans. The approach localises immune-stimulating proteins to tumours, avoiding damage to healthy tissues. Clinical trials could begin within two years.
CAR T-cell therapy, which genetically engineers immune cells to target cancer, has revolutionised treatment for blood cancers like leukaemia but has struggled against solid tumours. These tumours often feature diverse cell types lacking uniform mutant proteins and employ mechanisms to evade immune attacks, such as producing inhibitory signals.
To address this, Jun Ishihara and colleagues at Imperial College London enhanced CAR T-cells by fusing interleukin 12—a potent immune stimulator—with a collagen-binding protein. Tumours, like wounds, expose collagen in their structure, allowing the fusion to localise within the tumour. The modified CAR T-cells produce this fused protein only after binding to a specific mutant protein on prostate cancer cells, concentrating the interleukin-12 to trigger a targeted 'Attack! Attack!' response without widespread inflammation.
In experiments, the therapy eradicated large prostate tumours in four out of five mice. "The tumours were gone, completely gone," Ishihara said. Remarkably, the mice required no preconditioning chemotherapy, which typically depletes existing immune cells and can cause side effects like infertility. "We were actually surprised that we didn’t need the chemotherapy at all," he added. When reinjected with cancer cells, the mice did not develop new tumours, indicating a lasting immune response.
This marks the first time such complete eradication has been achieved in an animal study for solid tumours. Steven Albelda at the University of Pennsylvania called it "a promising approach that should be tested clinically," noting similar efforts by other groups. The findings appear in Nature Biomedical Engineering (DOI: 10.1038/s41551-025-01508-3), with Ishihara's team aiming for human trials in two years.