New research has identified genetic modifications that may increase the effectiveness of immunotherapy for multiple myeloma, a difficult-to-treat blood cancer most often diagnosed in people over 65.
- By MASS GENERAL BRIGHAM COMMUNICATIONS
A team led by scientists at Harvard Medical School, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard used CRISPR technology to pinpoint genes that could be edited to boost the efficacy of chimeric antigen receptor (CAR) T-cell therapy for cancer.
When the researchers edited those genes, they found that some of the modifications improved T-cell function and survival in a lab dish and in a mouse model of multiple myeloma.
The study, published Sept. 24 in Nature and supported in part by federal funding, describes a method that could help scientists more efficiently make improvements to CAR T-cell therapy.
"Testing individual genetic modifications to find those that enhance CAR T function would take a huge amount of time and money. Our approach lets us test hundreds of changes at a time," said co-senior author Marcela Maus, HMS professor of medicine at Mass General.
Although follow-up studies are needed to confirm the findings in humans, the scientists hope that their approach will eventually lead to better outcomes for patients with multiple myeloma - and can possibly be applied to other cancers.
Building better CAR T cells
CAR T-cell therapy is an immune-based treatment that involves retrieving a patient's T cells, modifying them, multiplying them, and reintroducing them into the patient to fight cancer cells. In recent years, the therapy has revolutionized treatment of blood cancers, including various forms of leukemia and lymphoma.
To date, CAR T-cell therapy has not been as effective against solid tumors or in patients with relapsed or treatment-resistant multiple myeloma. In addition, the number of CAR T cells circulating in the body decreases over time, limiting their long-term activity.
In the new study, the researchers developed a CRISPR screen that targeted 135 genes in human donor-derived CAR T cells to identify genes that may improve persistence and function. The team cultured the CRISPR-edited cells in a lab dish, transferred them into a mouse model of multiple myeloma, and tracked the animals' survival for up to 21 days.
