Despite success against other cancers, prostate tumours have so far resisted treatment with immunotherapy. But some researchers are persisting with the approach.
The first therapeutic cancer vaccine, approved more than a decade ago, targeted prostate tumours. The treatment involves extracting antigen-presenting cells — a component of the immune system that tells other cells what to target — from a person’s blood, loading them with a marker found on prostate tumours, and then returning them to the patient. The idea is that other immune cells will then take note and attack the cancer.
The gaps in the understanding of prostate tumours are a key obstacle to getting immunotherapy to work. “We haven’t done enough immune profiling of the prostate microenvironment in humans,” says Mark Linch, a uro-oncologist at University College London. “We’ve done a lot in mouse models, but these don’t recapitulate the most common type of prostate cancer.
Graff’s research hints at one potential approach. She and her colleagues showed that testosterone can limit the body’s response to immunotherapy — and therefore that therapy to reduce a person’s testosterone levels might boost cancer-fighting T cells. Hormone blockers are already commonly used in people with prostate cancer — almost all prostate tumours respond to this therapy initially, before resistance develops. Combination immunotherapies might have more success than one immunotherapy alone.
Various other combinations of vaccines and checkpoint inhibitors are being trialled. For example, Linch is working with biotechnology company BioNTech, headquartered in Mainz, Germany, on a clinical trial of an mRNA vaccine for prostate cancer, in which some participants will receive both the vaccine and a checkpoint inhibitor called cemiplimab that has been approved for skin cancer.
One BiTE currently under investigation is acapatamab , developed by pharmaceutical company Amgen in Thousand Oaks, California. This brings hooked T cells over to tumours by binding to PSMA. Even in people heavily pre-treated with other therapies, response rates in the phase I trial approached 33%. “That’s pretty exciting,” says Linch, who is now running a trial that combines acapatamab with a PD1 blocker or a hormone therapy.
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