By Pat Carragher - December 14, 2020
In 2017, Moffitt Cancer Center patient Rodney Rodriguez became one of the first patients whose acute myeloid leukemia (AML) went into remission as a result of chimeric antigen receptor T cell (CAR T) therapy.
“I was riddled with leukemia,” said Rodriguez. “But with CAR T – no chemo, no radiation, nothing else – it was gone in four weeks.”
Rodriguez was part of a phase 1 trial called the THINK study (THerapeutic Immunotherapy with NKG2D) – which looks at a CAR T therapy that genetically modifies immune cells to target leukemia tumors.
CAR T modifies a patient’s own immune cells to become better cancer fighters. Cells are removed from a patient’s blood and sent to a lab where the cells are genetically modified to better enable them to identify and attack cancer cells. Once the new cells are received, patients typically receive preconditioning chemotherapy to deplete their immune system and make room for the new cells. In the THINK study, no preconditioning chemotherapy was necessary.
According to Dr. David Sallman, an assistant member of the Department of Malignant Hematology, Rodriguez is still in remission to this day, but his success story has been one of few.
“We’ve continued to see responses. The challenge is the responses are not predictable and sometimes they don’t last,” Sallman said. “Despite optimizing the manufacturing, adding preconditioning and other changes, we have not increased the efficacy.”
Sallman believes part of the challenge is that the CAR T cells actually kill themselves instead of the cancer cells they were intended to kill, a process known as fratricide which may impact the expansion and persistence of the CAR T cells. While the results, which were presented at the American Society of Hematology Annual Meeting, aren’t what researchers had hoped, the THINK study has led the groundwork for future studies to build on its success with proof-of-principle activity shown when targeting NKG2D ligands.
“These were expected challenges going into it,” Sallman said. “It’s frustrating when therapy isn’t meeting the goal, but we’re having some successes.”
“We did some small expansion in the THINK study, but now it’s back to the dose escalation with the new product, CYAD-02, to think about moving forward to phase two or three but early clinical data are exciting,” Sallman said. “The novelty with this type of product is it’s not specific to one type of tumor. That’s important because we don’t have a perfect target with AML. We really need these responses to be durable. I’m still very hopeful within the next 3 to 5 years we’ll have a CAR T treatment for AML patients.”