A team led by Cold Spring Harbor Laboratory scientists Tobias Janowitz and Douglas Fearon together with Duncan Jodrell at the Cancer Research UK Cambridge Institute and Centre, University of Cambridge, UK, have reported the outcomes of a clinical trial of the drug plerixafor that induces an integrated immune response in the tumours of patients with pancreatic and colorectal cancer types that do not usually respond to immunotherapy. The researchers hope the potential treatment might make such tumours more responsive to the class of drugs known as immune checkpoint inhibitors.
The outcomes of the study, ‘CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response", were published in the Proceedings of the National Academy of Sciences.
Cancer immunotherapies, which empower patients' immune systems to eliminate tumours, are revolutionizing cancer treatment. Many patients respond well to these treatments, sometimes experiencing long-lasting remissions. But some cancers remain difficult to treat with immunotherapy and expanding the impact of the approach is a high priority.
Checkpoint inhibitors release natural brakes on the immune system, freeing it to find and destroy cancer cells, but they generally have not been effective against cancer cells with low levels of genetic mutation.
"Those tumours often do not seem to be visible to the immune system and do not seem to be unmasked by these therapies that are currently available,” explained Janowitz. “And we have reasons to believe that that is because they can engage an immune suppressive pathway that keeps most of the immune cells out of the cancer cell nest."
In this clinical trial, the research team interrupted that immunosuppressive pathway with plerixafor. The drug was intravenously administered continuously one week to 24 patients with either pancreatic cancer or colorectal cancer with a low tumour mutational burden. All patients had advanced disease, and biopsies were collected from metastatic tumours before and after treatment.
When the team analysed those patient samples, they found that critical immune cells had infiltrated the tumours during the time patients received plerixafor, including a cell type known to summon and organise key players in the anti-cancer response. The finding was encouraging because the team detected changes that have also been observed in patients whose cancers responded well to checkpoint inhibitors.
"I am delighted that the work of this multi-disciplinary team has translated important laboratory findings into patients, with the potential to make a difference in these hard-to-treat cancers,” added Jodrell.
A clinical trial based on this study is about to start recruitment and will test the effects of combining plerixafor with an approved checkpoint inhibitor.
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