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Ben Vincent, MD
Photo from the University
of North Carolina

New research could aid the development of immunotherapies tailored to patients with acute myeloid leukemia (AML) who are undergoing stem cell transplant (SCT).

Researchers found they could use genetic sequencing and computer software to identify minor histocompatibility antigens (mHAs) known to occur in AML.

The team used this method to predict novel graft-versus-leukemia (GVL) mHAs and demonstrated that one of these mHAs could be a “potentially useful” therapeutic target.

Ben Vincent, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, and his colleagues reported these findings in Blood Advances.

In their retrospective study, the researchers tested whether their software could predict antigenic targets in 101 SCT donor-recipient pairs.

The researchers found they could correctly identify 14 of 18 mHAs known to occur in AML, but they were also able to predict 102 new GVL mHAs.

The researchers then confirmed one of these GVL mHAs, called UNC-GRK4-V, as a potential target for immunotherapy. The team observed immune responses to UNC-GRK4-V in four of nine AML patients who had undergone SCT.

Looking ahead, the researchers want to optimize their software to predict the most common AML-associated mHAs present in the U.S. population and confirm these predicted antigens as valid immunotherapy targets.

The team believes they could potentially use their predictions to engineer donor immune cells to specifically target the cancer cell antigens while preventing graft-versus-host disease.

“We’ve developed a software package that predicts leukemia-specific immune targets in any leukemia patient undergoing a stem cell transplant based on DNA and RNA sequencing and demonstrated that these data can lead to actual targets expressed on leukemia cells,” Dr. Vincent said.

“The next step of our work is to use that information for patient-specific therapies to try to improve cure rates without making graft-versus-host disease worse.”

The current research was supported by a National Cancer Institute grant, an ASCO Young Investigator Award, the North Carolina University Cancer Research Fund, and the Scott Neil Schwirck Fellowship.

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