Sylvester Comprehensive Cancer Center shared on LinkedIn:
“Roughly 1 in 6 newly diagnosed large B-cell lymphomas carry a genetic deletion that can blunt one of the most powerful therapies available for the disease.
Researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, have identified loss of the RHOA gene as a driver of resistance to CAR T-cell therapy in large B-cell lymphoma.
The multicenter study was published in Blood Cancer Discovery, a journal of the American Association for Cancer Research, with Dr. Jonathan Schatz as senior author.
RHOA loss works on two fronts:
- lowers the tumor’s expression of CD19, the protein CAR T cells are engineered to recognize,
- weakens the tumor’s response to interferon gamma, an immune signaling molecule.
The combined effect reshapes the environment around the tumor so that engineered immune cells have a harder time finding and killing it.
‘One of the biggest challenges in cancer research is understanding why a treatment can be remarkably effective for some patients and fall short for others.
We wanted to understand what the tumor was doing to survive, and this study gave us a window into one of those survival strategies,’
said Dr. Jonathan Schatz, senior author of the study and professor of hematology at the Miller School of Medicine.
Because RHOA deletions can be identified in tumor tissue, the finding raises the prospect of flagging patients at higher risk of relapse before treatment begins.
It also points toward combination strategies that restore CD19 or interferon signaling, which the team describes as testable in the clinic.
You can also read: DESCAR-T: Real-World Outcomes After 2L CAR T-Cell Failure in Large B-Cell Lymphoma
