Moffitt Scientists Boost Cancer-Fighting Immune Cells

Researchers at Moffitt Cancer Center just figured out how to make cancer-fighting immune cells work harder and last longer in the body, a discovery that could transform treatment for some of the toughest cancers to fight.

The team, led by Dr. Daniel Abate-Daga, focused on improving CAR T-cell therapy, a treatment that turns a patient's own immune cells into powerful cancer destroyers. While this approach has revolutionized blood cancer treatment, it hasn't worked as well against solid tumors, especially cancers that spread to bone.

The breakthrough centers on a lesser-known type of immune cell called gamma-delta T cells. Unlike the alpha-beta T cells used in all FDA-approved CAR T treatments, gamma-delta cells have unique properties that make them safer and potentially more effective against bone cancers like metastatic prostate cancer.

The research team discovered something surprising when they compared both cell types in the lab. Gamma-delta cells killed cancer just as effectively as conventional cells, but they worked differently. They produced fewer inflammatory signaling molecules, which could mean fewer serious side effects for patients.

The team also found that gamma-delta cells used energy more slowly, which seemed to hold them back. So they did something clever: they identified a protein called TXNIP that was slowing the cells down and found two ways to reduce it, either with a drug or gene editing.

Both approaches worked beautifully. The modified cells produced more energy, displayed more cancer-targeting receptors, and generated more immune-boosting substances.

But the researchers didn't stop there. They added another upgrade by engineering the cells to recognize RANKL, a molecule found in bone and tumor environments. This modification worked like a homing beacon, helping the cells stay longer where tumors hide in the bone marrow.

When tested in mice with prostate cancer that had spread to bone, both regular and modified gamma-delta CAR T cells controlled tumor growth. But the modified cells remained in the bone marrow longer, suggesting they could provide more lasting protection against cancer.

Why This Inspires

This research represents a fundamental shift in how scientists approach CAR T therapy. Instead of treating all immune cells the same way, the Moffitt team showed that understanding each cell type's unique biology allows for customized improvements.

The implications reach beyond prostate cancer. The same approach could potentially help treat multiple myeloma and other cancers that spread to bone, conditions that currently have limited treatment options.

What makes this especially hopeful is that the researchers used multiple strategies that can be combined. They improved how the cells use energy, helped them stay where tumors hide, and potentially reduced side effects, all in one treatment.

The work moves CAR T therapy closer to becoming a viable option for solid tumors, which affect far more patients than blood cancers. If these modified cells prove safe and effective in human trials, they could offer new hope to thousands of people facing cancer that has spread to bone.