Siteman Cancer Center Research Leads to Clinical Trial
Advancements in treatment for acute myeloid leukemia (AML) are emerging as the result of promising translational research being performed by Washington University School of Medicine physicians and scientists at Siteman Cancer Center. AML is a cancer of blood-forming cells, which results in the bone marrow producing too few normal white blood cells, red blood cells or platelets. A dedicated team is investigating this therapy, which harnesses immune system cells from a donor related to the trial participant, to combat their cancerous cells.
Rizwan Romee, MD, the trial’s principal investigator and clinician, and Todd Fehniger, MD, PhD, the lead scientist, are currently overseeing the research and clinical trial, which is funded in part by the Specialized Program of Research Excellence (SPORE) in Leukemia grant. The trial uses cytokine-induced memory-like (CIML) natural killer (NK) cell based immunotherapy, which uses enhanced donor immune cells to treat patients with relapsed AML.
Through this unique activation strategy, these NK cells can potentially recognize, attack and clear cancer cells more robustly than the patient’s own immune system — providing outcomes that could be superior to existing AML treatments.
Patients who qualify for this trial have either failed to respond to traditional chemotherapy, or have relapsed AML. Current observations have shown the therapy to be well tolerated by the body, causing fewer side effects than traditional treatments. Immunotherapy could also provide a new option for patients who can’t tolerate other therapies, particularly if they are elderly and/or have additional health problems.
NK Cells: Antitumor Activation
The immunotherapy process begins by identifying a haploidentical, or “half match,” donor for the patient, typically a sibling, child or parent. As a “half match,” NK cells are able to recognize and destroy the patient’s leukemia cells. NK cells are then taken from the donor and activated overnight in a special biological therapy laboratory with several cytokines, which are protein hormones the immune system uses to communicate. The next day, the cytokine-activated cells are infused into the patient.
“Following the infusion, patients receive injections of cytokine for two weeks to promote NK cell growth,” says Dr. Romee. “Preliminary results, which we presented at the 2015 Annual Meeting of the American Society of Hematology, have shown some leukemia patients treated with CIML NK cells going into complete remission.”
What is now a promising clinical trial began with the discovery of memory-like properties of NK cells in mice, as the result of research conducted by Washington University immunologists that included Wayne Yokoyama, MD, and Megan Cooper, MD, PhD. Building on this, Dr. Romee and Dr. Fehniger began preclinical studies for the immunotherapy in 2011, after Dr. Romee identified that human NK cells also have memory-like properties. Several test tube and mouse model studies were able to successfully harness the cells’ antitumor functionality through cytokine activation. These promising results led to a clinical trial, just two short years later in 2014.
SPORE Support Brings Progress
“Our hope is that we can engineer these NK cells to respond to other types of blood cancer,” says Dr. Fehniger. “This clinical trial could lead to new avenues of immunotherapy, such as combining treatments with other immune-modulating drugs, or even genetically engineering cells to respond to different cancer types.” Soon, another clinical trial supported by SPORE will combine the CIML NK immunotherapy with a mini-transplant, as a less intensive alternative to traditional BMTs.
The current memory-like NK clinical trial, and its initial research, has been performed almost entirely at Siteman Cancer Center — currently the only facility in the country conducting this kind of trial. “It takes a dedicated team of both researchers and clinicians to bring a new treatment to AML patients. Some of our technical staff and trainees are in the biological therapy lab until 2 a.m. activating NK cells to give to patients the next day. It’s important to the entire team here; we know this work could have a great impact on an AML patient’s life,” says Dr. Fehniger.
Dr. Romee and Dr. Fehniger attribute much of the clinical trial’s progress to the financial support of the SPORE grant and to the trial participants. “Because of the patients who volunteer to participate in this clinical trial and in other trials at Siteman Cancer Center, we are able to make advancements in leukemia treatment that can lead directly to new therapy options for patients with this disease,” says Dr. Romee.
To learn more about this clinical trial, visit ClinicalTrials.gov, identifier: NCT01898793.