Researchers from the University of Sheffield have developed a groundbreaking nanoparticle-based immunotherapy that could significantly extend the effectiveness of hormone therapy for men with prostate cancer, according to findings published in the Journal for Immunotherapy of Cancer.
The Prostate Cancer UK-funded study demonstrates how this novel approach delays the onset of resistance to androgen deprivation therapy (ADT), a common first-line treatment for thousands of prostate cancer patients.
Understanding the Challenge of Treatment Resistance
For many men diagnosed with prostate cancer, ADT effectively limits cancer growth and spread initially. However, tumors frequently develop resistance to this treatment, allowing cancer to progress throughout the body and become incurable.
While immunotherapy has revolutionized treatment for many cancer types, its success has not translated to prostate cancer. This disparity has driven researchers to investigate the underlying mechanisms of resistance.
Professor Claire Lewis, who led the study at the University of Sheffield's School of Medicine and Population Health, explained: "The onset of resistance to hormone therapy is a major clinical problem when it comes to treating men with prostate cancer as their tumours then start to regrow and spread. Once this happens, their disease is difficult to treat and harsher treatments like chemotherapy have to be used."
Innovative Approach Using Nanoparticle Technology
The research team employed cutting-edge techniques to study immune cell function within prostate tumors, particularly following ADT treatment. Their analysis revealed that macrophages, a type of white blood cell, accumulate in large numbers around blood vessels in prostate tumors during hormone therapy.
This discovery led to the development of specialized nanoparticles that selectively deliver a drug to these macrophages, causing them to express interferon-beta, a potent immunostimulant. When released inside tumors, interferon-beta activates T cells to target and kill cancer cells, significantly delaying treatment resistance.
"Until now, immunotherapies for prostate cancer have been disappointing, with few men responding well to treatment," Professor Lewis noted. "Carefully analysing the way that immune cells in prostate tumours are inhibited by hormone treatment helped us to develop a way to overcome this and prevent resistance to hormone therapy."
Clinical Implications and Future Directions
The study represents the first demonstration that carefully designed nanoparticles can stimulate T cells to attack prostate cancer cells, potentially extending the effectiveness of hormone therapy.
Dr. Hayley Luxton, Research Impact Manager at Prostate Cancer UK, highlighted the significance of these findings: "Over 12,000 men die from prostate cancer each year in the UK, and we desperately need new and more effective treatments. Immunotherapy has completely changed the way other cancers are treated, but we haven't yet seen anything even close to that success for men with prostate cancer."
The research team is now collaborating with clinical colleagues to advance this promising therapy into clinical trials. If successful, this approach could transform treatment options for prostate cancer patients who develop resistance to hormone therapy.
Funding and Strategic Alignment
The study was funded through Prostate Cancer UK's Research Innovation Awards program, which has invested £20 million in innovative research over the past decade.
This work aligns with the University of Sheffield's cancer research strategy, which aims to reduce cancer-related deaths through high-quality research leading to more effective treatments and improved methods for cancer prevention, detection, and quality of life.
The published study, titled "Targeting a STING agonist to perivascular macrophages in prostate tumours delays resistance to androgen deprivation therapy," marks a significant step forward in addressing one of the most challenging aspects of prostate cancer treatment.
