Fusion Protein Immunotherapy: New Hope for Treating Rare Liver Cancer

T cells are white blood cells that detect and eliminate contaminated or malignant cells in the body. These immune cells locate their targets utilizing the T-cell receptor, which directs the cells to a specific protein on a tumor, similar to how law enforcement uses facial recognition to detect a criminal. The FLC-causing fusion protein is a dangerous fugitive in the body that is difficult to detect.

In 60-80% of cases, an FLC tumor cannot be physically removed, and even after treatment, the disease recurs, with patients dying within ten years. Outside of surgery, there are no effective medicines, prompting scientists to develop a new way. When the scientists implanted a T-cell receptor that identified the fusion protein in millions of T cells from mice with FLC-like tumors, the tumor size shrank dramatically, and all cancer cells expressing the fusion protein were destroyed.

In essence, the researchers swamped the tumor with immunological “law enforcement,” which was pre-programmed to recognize the fusion protein.

In humans, a comparable method known as T-cell receptor-transgenic (TCR-T) immunotherapy involves using a patient’s own T cells and adding the fusion protein-specific T-cell receptor. The modified T cells are then reintroduced to the patient, where they can locate and eliminate the tumor.

Finding a strategy to boost anti-fusion protein immunity
The study also indicates that, despite its rarity, the fusion protein can elicit a normal immune response. In fact, the researchers discovered only two natural T-cell responses to the fusion. Faced with this oddity, the researchers attempted to extrapolate from the two receptors to determine what others may be like.

“Once we’ve seen a few examples of a T-cell receptor that sees an antigen, we can usually predict others,” said senior co-corresponding author Paul Thomas, Ph.D., from the St. Jude Department of Host-Microbe Interactions. “We discovered that these two receptors did not look like one another or anything else we saw in the patient. So they were both distinctive.”

Such unusual results indicate that scientists are unlikely to discover another natural reaction to a preexisting tumor. “We tested many other patients and only ever found two T-cell responses, both from a single patient,” he said. “This is an incredibly rare response, so we were very lucky to find it.”

It is unknown what the best successful treatment for FLC will be, but discovering a single individual whose T cells can respond to the fusion has created new possibilities.

“In the end, we only found one patient with immune responses to the FLC fusion protein,” he stated. “But one may be just enough to push us forward into the next phase of developing more effective treatments for FLC.”

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