New Receptor Protein May Successfully Target Multiple Myeloma Cells
Posted: Thursday, March 19, 2020
Most patients with multiple myeloma eventually relapse after treatment. However, a novel chimeric antigen receptor (CAR) T-cell therapy showed promise in this patient population, in a study conducted by researchers at Huntsman Cancer Institute at the University of Utah, Salt Lake City. In laboratory tests with mouse models and patient tumor cells, the novel immunotherapy successfully targeted CD229, a molecule found on cancer cells in patients with multiple myeloma. The findings were published in Nature Communications.
“Although some of our patients respond quite well to currently available immunotherapies, they relapsed as early as 1 year after treatment,” Djordje Atanackovic, MD, stated in a University of Utah press release. “We thought if we could target every last cancer cell in a patient’s body, including the cancer stem cell, this could make the critical difference and yield more durable, deeper responses to treatment.”
This study was built on earlier work, in which the research team identified the CD229 target. After a series of tests, the research team chose the receptor protein 2D3. Using a mouse model and stem cells derived from patients with multiple myeloma, the researchers tested the efficacy of CD229 CAR T-cell therapy.
In laboratory tests, 2D3 selectively bound to CD229 and to cancer cells, but it did not bind to healthy cells. The protein also successfully bound to cancer cells that were isolated from the bone marrow of 20 patients with newly diagnosed or untreatable multiple myeloma. In the mouse model, the CAR T-cell therapy killed mature multiple myeloma cells and reduced cancer blood markers—and the treated mice experienced prolonged survival. Lastly, the researchers created an anti-CD229 CAR T-cell therapy by adding the receptor protein to T cells and found that the modified cells did not commit fratricide.
Further analyses are planned to test the therapeutic approach on human subjects.
Disclosure: For full disclosures of the study authors, visit nature.com.