Acute myeloid leukemia (AML) is an aggressive type of blood cancer that impacts both adults and children. Its incidence is increasing, especially in the United States and countries where people are living longer lives.
Researchers in the labs of immunologist Gianpietro Dotti, MD, and hematologist Paul Armistead, MD, PhD, have created a new cellular immunotherapy for AML that targets AML cells without impacting normal blood production, which is one of the major challenges associated with AML treatment. The development of this new therapy is reported in the journal Blood.
"We have implemented a multidisciplinary effort to identify a potentially safe target in AML," said Dotti, who is a professor of microbiology and immunology at the UNC School of Medicine and director of the UNC Lineberger Clinical Immunotherapy Program. "We developed the tools needed to engineer human T cells specific to the target and to identify the best mode of action for T cells to recognize very low levels of the target, while preventing leukemic cells from escaping T cell recognition."
Gianpietro Dotti, MD
Researchers in the Armistead and Dotti labs identified a peptide, CG1, that was highly abundant in AML and presented on the surface of AML cells by a molecule called HLA-A*02:01. Importantly, CG1 was not present on the surface of normal blood cells.
They next developed chimeric antigen receptor (CAR) T-cells to recognize and attack cells that express the CG1/HLA-A*02:01 complex. CAR T-cells are used as a type of immunotherapy treatment and are highly effective in treating other kinds of blood cancer such as B-cell lymphoma and multiple myeloma.
The therapy involves removing some of a patient's immune cells (T-cells), genetically modifying them to recognize a molecule on the cancer cell's surface, and then infusing them back into the patient. The CAR T-cells developed by Armistead and Dotti were able to effectively kill AML samples both in lab-dish models and in mice; however, the CAR T-cells did not kill normal blood cells
While CAR T-cells have been developed to treat AML, they have proven to be too toxic due to also targeting normal blood cells. It is hoped that targeting the CG1/HLA-A*02:01 complex will enable AML targeting without the same side-effects.
Their findings suggest CG1.CAR-T cells could be a promising treatment for AML.
