Our immune system is great at fighting many types of cancer, but it struggles to see prostate tumors. While new treatments have been game-changers for lung cancer and skin cancer, prostate cancer stays ‘hidden’ from the body’s defenses, failing to trigger the internal alarm needed for an attack.
Now, a cleverly engineered molecule has shown unprecedented early promise.
Prostate cancer is the most frequently diagnosed cancer among men in many countries, including the US and the UK. About 1.5 million men are diagnosed worldwide each year. The disease also carries stark racial disparities in outcomes, with Black men facing the highest incidence rate at roughly 194 cases per 100,000 people, compared to 119 for white men, 90 for Hispanic men, 82 for Native American men, and 65 for Asian and Pacific Islander men.
Scientists have reported results from an early-stage trial of an immunotherapy drug called VIR-5500. The drug offers new hope for men with advanced prostate cancer who have stopped responding to other treatments. The trial involved 58 patients across eight global sites.
The experimental treatment is a “T-cell engager.” It works by forcing a handshake between the body’s killer T-cells (immune cells that attack foreign cells, cancer cells, and cells infected with a virus) and the tumor cells trying to hide from them. By latching onto both the immune cell and a specific protein on the cancer cell’s surface, the drug brings the two into lethal contact.
“T-cell engagers empower the body’s own immune system to give cancer cells the kiss of death,” said Professor Johann de Bono of the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, who led the work.
A molecular Trojan horse
Historically, deploying T-cell engagers against prostate cancer has triggered severe, widespread inflammatory responses. These drugs activate the immune system indiscriminately, causing collateral damage that is often too high for patients to tolerate.
VIR-5500 navigates this problem by acting as a molecular Trojan horse. The drug features a unique “cloaking device” that keeps it hidden and inactive until it physically reaches the tumor site.
This precision minimizes adverse reactions and allows the medicine to linger longer in the bloodstream. Consequently, patients may require fewer doses. Among the men tested in the phase one clinical trial, funded by Vir Biotechnology, 88% experienced only very mild side effects.
“It’s very positive to see that very few patients have experienced major side-effects, as this has been a key challenge in treating prostate cancers with immunotherapies in the past,” De Bono noted.
The trial results, presented at the American Society of Clinical Oncology Genitourinary Cancers Symptoms, revealed significant responses. Researchers looked at prostate-specific antigen (PSA), a blood biomarker that indicates prostate disease.
Among 17 men given the highest dose, 82% saw their PSA levels fall by at least half. Furthermore, 53% experienced a 90% drop, and 29% saw their levels plummet by at least 99%.
De Bono described the results as unprecedented for a disease previously thought to be resistant to immunotherapy. “We do need more data but the results are stunning,” he said.
Shrinking tumors, expanding hope
Some of the recoveries have been stunning. Of the 11 high-dose patients with measurable tumors, 45% saw their tumors physically shrink on scans.
In one case, a 63-year-old man entered the trial with cancer that had metastasized to his liver. After six cycles of the therapy, 14 cancerous liver lesions were “completely resolved.”
Another 70-year-old participant experienced a total regression of small tumors outside his prostate, reporting an “excellent” quality of life. Meanwhile, a 77-year-old man saw his PSA drop to “undetectable” levels after 17 cycles.
Professor Kristian Helin, chief executive of the Institute of Cancer Research, London, noted the historical significance.
“Immunotherapy has transformed the outcomes for many people with cancer but for those with prostate cancer its benefits have often remained out of reach,” Helin said. “It’s encouraging to see this innovative approach showing promising effects in early clinical studies.”
As the drug moves toward larger trials, experts emphasize the need for diverse patient enrollment. Charlotte Bevan, a professor of cancer biology at Imperial College London who was not involved in the work, called the advance potentially very exciting. However, she added that it was important studies were carried out with patients of different ethnicities due to disparities in outcomes.
Patient advocacy groups are similarly eager. Simon Grieveson, assistant director of research at Prostate Cancer UK, stressed the high stakes.
“These early results are extremely promising, with a number of men on the study responding positively to the treatment with minimal side effects,” Grieveson told The Guardian. “I look forward to seeing this now tested in larger trials, with the hope that this treatment will offer men more valuable time with their loved ones.”