Smart Drug That Strips Cancer Cells of 'Invisibility Cloak' Can Shrink Tumours by 30%, Trial Shows

Breakthrough Cancer Drug Reveals Hidden Tumors

A smart drug that stops cancer cells "hiding" from treatment can shrink tumours by at least 30% in six of the world's most common forms of the disease, according to early trial results. While immunotherapy treatments have improved survival rates for many patients, their effectiveness can stall or fail when tumour cells hide and then spread.

How the Smart Drug Works

Researchers in Oxford have developed a drug designed to stop cancer cells concealing themselves from the immune system, allowing immunotherapy treatments to identify and destroy them. In a trial spanning the UK, France, Spain and Australia, 83 patients with cervical, bladder, liver, bowel, lung or head and neck cancers were given the experimental drug, GRWD5769, alongside the immunotherapy treatment cemiplimab.

The smart drug was able to remove "invisibility cloaks" from tumour cells, exposing them to the parts of the immune system that attack infections and diseases. This allowed the cemiplimab immunotherapy to pinpoint and destroy the cancer.

Trial Results Across Cancer Types

Researchers, led by the Christie NHS foundation trust in Manchester, England, found that tumours shrank in 26 patients. Of those, 15 experienced tumour reductions of at least 30%. All participants had previously failed to respond to treatment, and most had no options left when they joined the study.

GRWD5769 was shown to shrink tumours in all six cancer types included in the trial. The drug halted progression of the disease for at least six months in 18% of cervical cancer patients, 32% of liver cancer patients, 36% of bladder cancer patients, 38% of those with neck and head cancer, and more than half of bowel (51%) and lung (55%) cancer patients.

Significance for Cancer Treatment

Immunotherapy enlists T-cells – immune system cells that attack infections and diseases – to hunt and destroy cancer. Although it has revolutionised cancer care, it fails in about two-thirds of patients. This is because immunotherapy struggles when tumours hide from the immune system.

Tumours can evade the immune system by manipulating an enzyme called ERAP1 (endoplasmic reticulum aminopeptidase 1). By altering this enzyme, cancer cells can hide from a patient's T-cells. GRWD5769 solves this problem by inhibiting ERAP1, which removes cancer's invisibility cloak and makes tumour cells visible to T-cells that could not previously find them.

Future Outlook for Cancer Treatment

The findings were presented at the American Society of Clinical Oncology's annual meeting in Chicago, the world's largest cancer conference. Prof Fiona Thistlethwaite, the principal investigator, noted: "For a drug that is given as a tablet, this is very impressive. It's early days, and we need further studies, but this is a new drug with a new mechanism that clearly helps immunotherapy perform more effectively."

The tablets, which were developed by Oxford-based Greywolf Therapeutics and were tolerated well by patients. The trial remains ongoing, with a larger study planned. Cancer Research UK's research information lead, Dr Samuel Godfrey, noted: "Immunotherapy has transformed treatment for some cancers but it doesn't yet work for everyone. This trial seems to show how this new drug could make immunotherapy more effective, including in some cases where immunotherapy had previously failed."