University of Colorado Cancer Center member M. Eric Kohler, MD, PhD, was awarded a three-year, $270,650 Young Investigator Grant from CureSearch for Children’s Cancer, in partnership with the SebastianStrong Foundation, to develop a new treatment approach for acute myeloid leukemia (AML), a rare blood cancer in children.
While improved treatment options for pediatric leukemia have increased patient survival rates, certain subtypes will not be cured with conventional chemotherapy. AML patients who do not respond to treatment, or experience recurrence after treatment, usually survive fewer than six months. Kohler’s research aims to improve the prognosis by using CAR T-cell therapy, in which a patient’s immune cells are removed from the body, reengineered to seek out and destroy cancer cells, and then reinfused into the patient.
Kohler is one of several CU Cancer Center researchers regarded as national leaders in CAR T-cell therapy. His early research with the therapy focused on acute lymphoblastic leukemia (ALL), but with the new grant, he plans to continue his research on using CAR T-cell therapy against AML as well.
“It’s been my focus for the last several years to transition what we’ve learned about CAR T-cells in ALL and apply it to AML,” he says. “The heart of this grant is addressing the challenges of adapting from what we are doing to what we need to do next. It’s not just plug-and-play and use the exact same strategy again. With AML, we really have to rethink CAR T-cells from the ground up.”
Broadening the immune response
CAR T-cell therapy is ideal when a patient’s disease no longer responds to chemotherapy, as it relies on the immune system to eliminate leukemia cells. Kohler will develop two CAR T-cell approaches for AML, which will decrease the leukemia cells’ ability to avoid treatment and reduce toxicity in children with relapsed AML.
“The first approach is what I think of as broadening the CAR T-cell response, so that we can really target all the leukemia cells,” Kohler says. “The second part of the grant is focused on going after new targets on specific populations of AML cells that are thought to drive these relapses and resistance to conventional therapies.”
At the conclusion of the three-year project, Kohler aims to move these new immunotherapy strategies into early-phase clinical trials. If successful, this novel approach can potentially be applied to other forms of childhood cancers with poor prognoses.
“CAR T-cells have revolutionized the treatment of pediatric patients with relapsed ALL,” says Kohler, a pediatric oncologist at Children’s Hospital Colorado. “Through this award from CureSearch and the SebastianStrong Foundation, we have the opportunity to reimagine CAR T-cell therapies to meet the needs of children and young adults with AML.”
Innovation in action
Kohler’s research was selected as a recipient of the SebastianStrong Foundation’s annual Discovery Science Award. The award is granted to research projects that use innovative methodologies and out-of-the-box approaches in the quest for less-toxic cures.
“I’m extremely grateful and a little humbled that they chose this project to fund,” Kohler says. “As a young investigator, these grants are critical to taking my research from concepts to experiments and testing and then, hopefully, to new therapies for patients.”