Seattle Children’s hospital is working on a new approach aimed at making reprogrammed immunotherapy cells stay active longer.
The hospital has had success using immunotherapy to treat pediatric leukemia, but it has not proved long-lasting for all patients, with the cancer recurring within a year for about half of patients.
To fight pediatric leukemia, Seattle Children’s researchers work with T-cells, the immune system’s warrior cells that attack everything from viruses to cancer. Doctors at the Ben Towne Center for Childhood Cancer Research take T-cells from a patient and modify them with chimeric antigen receptors, or CAR. The resulting CAR T-cells are better able to target cancer cells.
“We've achieved phenomenal remission rates with that therapy. More than 90 percent of our kids have gotten into remission. These are kids that were resistant to traditional chemotherapy,” said Dr. Colleen Annesley, an oncologist at Seattle Children’s and the lead investigator of the latest trial called PLAT-03.
Annesley says the first study called PLAT 2 had a 93 percent success rate, but about half of those children experienced a recurrence of their cancer.
With this new trial, they hope will reverse those odds.
“This new trial, PLAT 3, it's a successor trial to PLAT 2 and will be a first in human trial, and we are re-engineering another group of T-cells," said Annesley. "These are going to be called T antigen presenting cells, and they're going to look like the leukemia cells.”
The idea is to use that second set of T-cells to fool the first set of T-cells into thinking the leukemia is still active.
“We are almost tricking the CAR T-cells to think the leukemia is coming back, so the same thing that the CAR T-cells recognize on the surface of the leukemia cells that makes them kill the leukemia cell. We are giving that protein. We are showing that protein again to the CAR T-cells through this new set of cells,” said Annesley.
The theory is that the CAR T-cells will continue to fight cancer before a full-on recurrence can start.
“We think the longer persistence of the CAR T-cells will lead to improved outcomes and overall increased survival and decreased recurrence rate of leukemia,” said Annesley.
Doctors at Seattle Children’s are now recruiting up to 30 patients to undergo the PLAT 2 therapy of re-engineered CAR T-cancer-fighting cells with the addition of PLAT 3 cancer mimicking cells a short time later.
“The CAR T-cells usually don't peek until roughly seven to 14 days after giving them, and then we wait for patients to recover from any side effects they may experience from the CAR T-cells. Once they've recovered we plan to start giving them these new cells,” said Annesley.
Patients experience inflammation in their body as their immune system fights off cancer, and this is a good sign that the therapy is working.
“We think the longer the CAR T-cells last and persist, it's a protective effect that this will decrease the risk of leukemia returning, and ultimately our goal is to provide a long-term cure for all of these children, and this is just the first strategy that we develop to try to make that happen,” said Annesley.
The research team led by Dr. Mike Jensen at the Ben Towne Center for Childhood Cancer Research is hoping to begin this new therapy in June to early July.
It should be a few weeks later when they’ll know how successful the PLAT 3 Trial will be.