Existing Drug May Overcome Immunotherapy Resistance in Rare Liver Cancer
Study finds FDA-approved drug AMD3100 can mobilize immune T cells to attack fibrolamellar carcinoma, a rare liver cancer affecting children and young adults that has resisted immunotherapy treatment.
A new study finds an existing FDA-approved drug may allow immunotherapy to fight fibrolamellar carcinoma as intended, opening the door to a potential treatment for a rare and fatal liver cancer that has resisted immunotherapy.
Fibrolamellar carcinoma primarily affects children and young adults and accounts for up to 2% of all liver cancers. It currently has no cure and has often metastasized by the time it is detected, leaving patients with a short life expectancy.
The study, published Feb. 17 in the journal Gastroenterology, describes how fibrolamellar tumors rewire their local microenvironments such that the body's immune T cells become sequestered away from the cancer cells where they can't fight the disease—a process called T-cell exclusion. The researchers also found that AMD3100, a drug currently used to treat a different disorder, can prevent the tumors from sequestering T cells, freeing them to attack the cancer.
The results provide among the first indications of why a type of immunotherapy called immune checkpoint inhibition hasn't worked well in these patients. The tumor microenvironment and T-cell sequestration provide clues to why some cancers don't respond to immune checkpoint inhibitors.
Normally, when clinicians administer immune checkpoint inhibitors, they activate the body's own immune T cells to migrate to the core of the cancer to try and kill the tumor cells. Immune checkpoint inhibitors can be highly effective against liver, lung, kidney and bladder cancers, as well as melanoma, but many cancers—pancreatic, prostate, brain—can be resistant.
Researchers used patient tumor slices to test AMD3100 and found that it effectively mobilized T cells into the core of the tumor. Moreover, combining AMD3100 together with immune checkpoint inhibition further facilitated activation of T cells, leading to a significant increase in the death of tumor cells.
Researchers are currently searching for liver cancer clinicians who might be interested in starting clinical trials for the new treatment. A compelling feature of this work is that AMD3100 is already FDA-approved, which can reduce risks and potentially speed up timelines for clinical trials in fibrolamellar carcinoma.