Genetically modifying immune cells might effectively treat multiple myeloma, according to a new study. The researchers modified T cells to target the molecule CS1, which is found on more than 95% of myeloma cells, and then to kill the cells. The researchers grew the modified cells in the lab to increase their numbers and then injected them into an animal model where they again killed human myeloma cells.
Multiple myeloma is a cancer of the blood that is still incurable, and new therapies are urgently needed. Multiple myeloma will account for an estimated 24,000 new cases and 11,100 deaths in 2014.
“Despite current drugs and use of bone marrow transplantation, multiple myeloma is still incurable, and almost all patients eventually relapse,” said coprincipal investigator and multiple myeloma specialist Craig Hofmeister, MD, MPH, assistant professor of medicine and a member of the Ohio State University Comprehensive Cancer Center–James (OSUCCC–James) Translational Therapeutics Program in Columbus.
“This study presents a novel strategy for treating multiple myeloma, and we hope to bring it to patients as part of a phase I clinical trial as soon as possible,” Hofmeister said.
“In particular, our study shows that we can modify T lymphocytes to target CS1, and that these cells efficiently destroy human multiple myeloma cells,” said principal investigator Jianhua Yu, PhD, assistant professor of medicine and a member of the OSUCCC–James Leukemia Research Program.
“An important possible advantage to this approach is that these therapeutic T cells have the potential to replicate in the body, and therefore they might suppress tumor growth and prevent relapse for a prolonged period,” Yu said.
For this study, Yu, Hofmeister, and their colleagues used cell lines and fresh myeloma cells from patients to produce genetically engineered T cells with a receptor that targets CS1. The researchers then tested the capacity of the modified cells to kill human multiple myeloma cells in laboratory studies and an animal model. The findings were published in Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-13-2510).
The study found that, compared to control T cells, the modified T cells better recognized multiple myeloma cells that overexpressed CS1, and they became more activated following the recognition. Fresh T cells from patients were successfully modified and expanded in the laboratory, and these were able to efficiently recognize and eradicate myeloma cells.
In animal models, the modified T cells greatly reduced the tumor burden and prolonged overall survival. All the mice that received the modified T cells were alive at 44 days after treatment; however, only 29% and 17% of the mice in the two control groups were alive 44 days later.