In a study from Cold Spring Harbor Laboratory, scientists found a drug that induces an integrated immune response in the tumors of patients with cancer types that do not usually respond to immunotherapy.
They hope the potential treatment might make such tumors more responsive to the class of drugs known as immune checkpoint inhibitors.
Cancer immunotherapies, which empower patients’ immune systems to eliminate tumors, 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 tumors 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.
And scientists 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 study, researchers interrupted that immunosuppressive pathway with a drug called plerixafor.
The drug was administered continuously by I.V. for one week to 24 patients with either pancreatic cancer or colorectal cancer with a low tumor mutational burden.
All patients had advanced disease, and biopsies were collected from metastatic tumors before and after treatment.
When the team analyzed those patient samples, they found that critical immune cells had infiltrated the tumors during the time patients received plerixafor, including a cell type known to summon and organize 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.
A clinical trial based on this study will test the effects of combining plerixafor with an approved checkpoint inhibitor.
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The study was conducted by Tobias Janowitz et al and published in the Proceedings of the National Academy of Sciences.
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