Protein-Inhibiting Therapy May Reduce Stem-cell Transplant Complication GVHD

Protein-Inhibiting Therapy May Reduce Stem-cell Transplant Complication GVHD

Researchers are a step closer to preventing graf-versus-host-disease (GVHD), a common life-threatening complication in patients receiving stem-cell transplants.

In a new study, a novel therapy that inhibits two proteins involved in T-cell activation, Aurora A and JAK2, prevented GVHD in mice without affecting the immune system’s ability to fight infections or tumor cells.

The research, “Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining Treg and antitumor CTL function,” was published in Science Translational Medicine.

Stem cell transplants are the only way to cure patients with lymphoma or leukemia, but like most therapies, it comes with risks.

Because most patients receive stem cells donated by another person — called allogeneic transplants — they are at risk of developing GVHD. This complication occurs when the transplanted immune cells recognize the patient’s own tissues and organs as foreign. It is the leading cause of non-relapse-associated death in patients who receive transplants.

Researchers have long been trying to reduce the risk of GVHD. Apart from choosing a donor whose tissue type closely matches the patient’s, doctors give patients preventive drugs that suppress the immune system during the transplants.

However, patients may still develop GVHD. Because the immune system is broadly shut down by the immunosuppressors, they have increased risk of serious infections — and the donor cells cannot fight the patients’ residual tumor cells.

In an attempt to develop better treatments to prevent GVHD, without affecting the patient’s ability to fight infections or tumor cells, researchers at the Moffitt Cancer Center focused on the proteins Aurora A and JAK2.

“It is known that Aurora kinase A and JAK2 pathway activation contributes to GVHD. However, drugs that inhibit either protein alone do not completely prevent GVHD,” Brian C. Betts, MD, the study’s lead researcher, said in a press release. “We hypothesized that co-treatment with drugs that target both Aurora kinase A and JAK2 could prevent GVHD better than either drug alone.”

As expected, when the researchers used a Moffitt-developed treatment to inhibit both Aurora A and JAK2, GVHD was significantly reduced in mice. But importantly, this did not affect the development and activity of anti-tumor T-cells.

“This novel prevention strategy warrants further investigation because of its potential to reduce the risk of GVHD and possibly be more effective and selective than commonly used GVHD treatments currently available today,” Betts said.

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