In a new study, researchers found that an injectable drug used to reduce stubbornly high cholesterol levels appears may also enhance the immune response of anti-cancer therapies known as immune checkpoint inhibitors.
Based on the findings, human studies are already being proposed to determine whether cholesterol drugs such as evolocumab (sold as Repatha) or alirocumab (Praluent) might bolster the effect of immune checkpoint inhibitors.
These cancer immunotherapies have held great promise, but still only result in long-term survival benefits for a third of cancer patients, at most.
The research was conducted by a team at Duke Health.
The team built on previous studies showing that higher amounts of active T cells improve the success of immune checkpoint blockade therapies, and that lowering blood cholesterol also appears to improve cancer immunotherapies.
The question they sought to resolve was whether the PCSK9 protein was involved in regulating tumor response to immunotherapy, since it is a key regulator of serum cholesterol levels.
In studies of mouse tumor models, they used CRISPR gene editing techniques to delete the PCSK9 gene and found that this slowed tumor growth.
When they implanted these edited tumors in immunocompromised mice—animals without T-cells—the tumors grew just as fast as normal tumors in normal mice, suggesting that T-cell activity is needed for the PCSK0-neutralizing drugs to have an impact on tumors.
The anti-cholesterol drugs appear to increase the amount of a protein on the tumor cell surface that signals T cells to recognize tumor cells.
This led to a robust attack on the tumor, overcoming one of the key impediments to the success of immunotherapies when the body’s T-cells are often inactivated, exhausted, or unable to recognize tumor cells.
As a result, the capacity of the anti-PCSK9 drugs to boost immunotherapy is independent of their abilities to lower cholesterol.
Analysis of previously published human data also suggests that PCSK9 protein may potentially be a good target in several other types of cancers including those of liver, lung, and kidney origins.”
One author of the study is Chuan-Yuan Li, a professor in Duke’s departments of Dermatology and Pharmacology and Cancer Biology.
The study is published in Nature.
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