Currently Approved Drug Could Boost Immunotherapy Against Liver Cancer

Researchers at University of Washington have discovered that a drug that is currently approved by the FDA could help in boosting the efficacy of immunotherapy against a rare type of liver cancer that has previously been unresponsive to checkpoint inhibitors. 

The preclinical study, whose findings appeared in the Gastroenterology journal, found that fibrolamellar carcinoma, an aggressive type of liver cancer, alters normal liver cells and causes them to produce the fibrous tissue that is characteristic of this type of cancer. T-cells that are meant to fight the cancer are then rechanneled into these fibrous bands and trapped there. 

As a result of this entrapment, the body’s immune system is unable to combat the cancer cells and any immunotherapy administered to patients is rendered ineffective. 

To arrive at their findings, the team leveraged advanced technology called single-nucleus transcriptomics to study individual nuclei inside tumors to understand the genes acting in each of those cancer cells. Through this method, the researchers were able to get rare insights into how cancer cells operate. 

They learned that cancer cells undertake what is called T-cell exclusion, a process through which fighter immune cells are prevented from reaching the tumor microenvironment to wage a meaningful attack against the cancer. 

Once they identified this mechanism, they went about searching for a drug that could block cancer cells from performing T-cell exclusion. They discovered that a drug, called AMD3100, a compound that already has FDA regulatory approval for use in another condition, could block cancer cells from excluding T-cells from the tumor microenvironment. 

When AMD3100 was applied to tumor tissues, the liver cancer’s progression was significantly slowed due to the immune system’s attacks against tumor cells. When this compound was administered alongside an immunotherapy, the results were even more impressive, proving that the treatment approach they had developed could potentially transform the fight against fibrolamellar carcinoma. 

The finding offers a previously unknown explanation for why some cancer types resist checkpoint inhibitor therapies, and how that resistance can be overcome. 

The team is now seeking collaborations with interested biomedical entities to move these findings into clinical trials as a necessary step before the method can become available to patients diagnosed with this rare cancer. 

One big advantage of this approach is that it uses a drug that already has regulatory approval, so the time needed to take it through clinical testing for liver cancer is bound to be a lot shorter. Attendant costs involved in this testing process are also bound to be lower since the needed treatment isn’t being developed from scratch. 

While this study focused on fibrolamellar carcinoma, other types of cancer are also getting unprecedented levels of research attention from companies like Calidi Biotherapeutics Inc. (NYSE American: CLDI). Checkpoint inhibition therapy against cancer is therefore likely to advance rapidly over the next few years. 

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