For acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients who don’t respond to treatment or who have relapsed, there are limited treatment options. The average survival rate is less than six months, creating a need for new, fast treatment options.

Chimeric antigen receptor T-cell therapy, or CAR T, is one of the more recently approved immunotherapies approved by the U.S. Food and Drug Administration. The treatment involves removing a patient’s T cells from their blood and modifying them in a lab to recognize and destroy cancer cells once infused back into the body.

CAR T therapy has produced durable remission for patients with acute lymphoblastic leukemia and lymphoma, but is not approved for AML and MDS patients and has shown limited success in clinical trials. While the CD33 antigen is highly expressed in most AML patients and could be a target for CAR T cells, there are barriers to the treatment being successful, including challenges with efficacy, potential toxicity and a long manufacturing period.

“These patients are often critically sick with severely low blood counts,” said Dr. David Sallman, a hematologist in the Malignant Hematology Program at Moffitt Cancer Center. “A lot of these patients can’t wait for a traditional CAR T cell manufacturing process that takes three to four weeks.”

"These patients are often critically sick with severely low blood counts. A lot of these patients can’t wait for a traditional CAR T cell manufacturing process that takes three to four weeks."

- Dr. David Sallman, a hematologist in the Malignant Hematology Program

A phase 1b study that was presented at the American Society of Hematology annual meeting looks at the safety and efficacy of a new type of CAR T called UltraCAR-T™ therapy for myeloid malignancies. UltraCAR-T cells express CD33 and membrane bound IL-15. And unlike current CAR T cells, which utilize viruses to attach the CAR to the T cells, UltraCAR-T uses a non-viral gene delivery system and a rapid manufacturing process.

“It is a very rapid turnaround from taking the patient’s cells out of their body and giving them back as quickly as two days later,” said Sallman, the trial’s principle investigator. “It is also adaptable, so down the road if we want to target more than one antigen that would be possible with this technology.” 

The study is testing if UltraCAR-T is safe and effective for two sets of myeloid patients: those who receive lymphodepleting chemotherapy prior to the treatment and those who don’t. So far, low dose levels of the treatment have showed promising results with good safety, no manufacturing failure and some early evidence of clinical activity. UltraCAR-T also has a kill switch for safety. Because all of the main targets for MDS and AML are also expressed on normal stem cells, there is a concern the treatment could also attack healthy cells and eliminate the body’s ability to make blood. The kill switch would stop the treatment and eliminate the CAR if ultimately needed.

After the phase 1 test groups have completed treatment, the goal is to expand the trial to other cancer centers to accrue more patients.