Upstate immunologist Mobin Karimi, MD/PhD, has been awarded a $3.3 million grant to explore a new type of immunotherapy to treat acute myeloid leukemia.
The grant comes from the National Cancer Institute of the National Institutes of Health.
Karimi, an assistant professor of microbiology and immunology, is the principal investigator on the study, called, “Harnessing β-Catenin and NKG2D to Enable HLA-Independent CD8⁺ T-Cell Immunotherapy Against Acute Myeloid Leukemia.”
The study runs through July 2031.
Acute myeloid leukemia (AML) is an aggressive blood cancer that remains difficult to treat with immunotherapy. One major challenge is that AML cells can reduce proteins called HLA class I, which are normally needed for immune cells to recognize and attack cancer cells.
“Our research has identified another way that these immune cells may recognize leukemia cells without relying on HLA,” Karimi said. “In this study, we aim to understand how the alternative pathway is regulated in immune cells from patients with AML and how this pathway could be strengthened to improve immune-based treatments for leukemia.”
Karimi said the goal of this project is to understand how modified immune cells can recognize and attack acute myeloid leukemia (AML) without depending on HLA. AML develops mainly in the bone marrow, where leukemia cells can create an environment that helps them hide from the immune system and avoid being recognized by cancer-fighting immune cells.
“We want to understand the mechanisms AML cells use to escape immune detection and weaken these modified immune cells,” he said. “By identifying these escape strategies, we hope to find ways to overcome them and improve the ability of immune cells to recognize and destroy AML. Ultimately, this knowledge could help us develop more effective HLA-independent immunotherapies for patients with AML.”
AML cells can alter the immune environment in ways that make it difficult for a patient’s own immune cells to recognize and destroy the leukemia. For some patients, especially those with high-risk or relapsed AML, doctors may use an allogeneic stem cell transplant, which provides a new immune system from a donor.
“These donor immune cells can recognize and attack the leukemia, producing what is called a graft-versus-leukemia effect,” he said. “However, the same donor immune cells can also attack the patient’s healthy tissues. This serious complication is called graft-versus-host disease, or GVHD.”
No treatments for GVHD are available, severe GVHD can be difficult to control and can cause significant illness and death.
“Therefore, one of our major goals is to develop immune cells that can effectively attack AML while avoiding damage to healthy tissues,” Karimi said. “We will use this knowledge as a foundation to develop new immune-based therapies that can ultimately be translated directly to patients with AML.”