Researchers call on Sleeping Beauty to arm T cells against cancer #ASH13
When it comes to equipping T cells, the immune system's attack dogs, to find and kill cancer cells, Sleeping Beauty just might be a heroine in the story.
Genetically altering T cells to recognize a surface protein called CD19 and destroy cells that wear it has shown great promise for treating blood cancers, most recently in clinical trials presented during this week at the 55th American Society of Hematology (ASH) Annual Meeting in Exposition, now under way in New Orleans.
Encouraging early results from the first clinical trials of T cells modified by gene transfer using the Sleeping Beauty transposon to deliver a genetic package that creates an anti-CD19 receptor on T cells were reported Sunday night at ASH.
"Five months into these clinical trials, no acute or late toxicities have been noted from treatment with genetically modified chimeric antigen receptor (CAR) T cells in nine patients after they received blood stem cell transplantation," says Partow Kebriaei, M.D., associate professor of Stem Cell Transplantation and Cellular Therapy.
"Delivering CAR T cells after transplant targets minimal residual disease in hopes of maintaining remission for people with high-risk B cell malignancies," Kebriaei says.
Of the first five patients with acute lymphoblastic leukemia, three treated with the initial, minimal T cell dose had their disease progress while the first patient treated at the next highest dose remains in remission. It was too early to evaluate the fifth, who received an umbilical cord blood transplant.
Four non-Hodgkin lymphoma patients treated with the higherT cell dose all remained in remission after three months. Eventually, 25 patients will be treated in the clinical trial.
Most techniques place new DNA to a patient's own T cells using a viral delivery method. The Sleeping Beauty approach developed by an MD Anderson team led by Professor of Pediatrics Laurence Cooper, M.D., Ph.D., promises to be faster, simpler and therefore a more nimble process for customizing T cells, as well as far less expensive.
The Sleeping Beauty approach was created by Perry Hackett, Ph.D., professor of Genetics, Cell Biology and Development at the University of Minnesota. The MD Anderson clinical trials are the first-in-human application of the technique, with the T cells created in Cooper's lab.
The researchers have opened a new clinical trial to treat people with B cell malignancies with CAR T cells right after they finish chemotherapy.
"The goal here would be to actually avoid stem cell transplant," Cooper said. Plans for solid tumor trials are in the works.
This approach is proceeding under MD Anderson's Moon Shots Program to accelerate the pace of converting scientific discoveries into clinical advances that reduce cancer deaths.
ASH Abstract 166
MD Anderson news release