The results of a new T cell therapy study entitled “T Cells Engineered with a Chimeric Antigen Receptor (CAR) Targeting CD19 (CTL019) Have Long-Term Persistence and Induce Durable Remissions in Children with Relapsed, Refractory ALL” showed high potential in treating children with aggressive forms of acute lymphoblastic leukemia (ALL). The results were recently presented during the American Society of Hematology (ASH) Annual Meeting, in San Francisco.
ALL is a type of B cell cancer, such as non-Hogdkins lymphoma and chronic lymphocytic leukemia (CLL), and is the most common form of leukemia affecting children (responsible for 30% of all paediatric cancers).
In this pilot study, a group of 39 children diagnosed with ALL were treated with bioengineered T cells. Specifically, this T cell therapy consisted of retrieving T cells from a patients’ blood and genetically modifying them to express a protein that enhances their capacity to bind to a target CD19, a protein present only at the surface of B cells.
The re-engineered T cells (CTL019 cells) are introduced back into the patient, where they multiply and are capable of finding and destroying B cells. Additionally, CTL019 cells remain in the body for long periods of time, therefore continuing the surveillance and destroying any cancerous B cells that appear after treatment.
Among the 39 children, 92%, or 36, had a complete response to the therapy within one month of treatment, with 69%, or 25, showing remission six months after treatment, as assessed during the follow-up. The authors registered 10 relapses, 5 of them fatal, among the 36 children with complete responses.
Importantly, the cell therapy with CTL019 cells destroys both cancerous and healthy B cells, since the CD19 receptor is present in both subsets. Additionally, they stimulate cytotoxic production of cytokines (important immune signalling molecules) leading to a phenomenon previously described as cytokine release syndrome.
Thus, to counteract this cytotoxic effect, the authors added an immunomodulating drug. As such, to overcome the loss of healthy B cells, patients undergoing T cell therapy had to be administered with infusions of immunoglobin.
Stephan A. Grupp,M.D.,Ph.D., lead author of the study, a pediatric oncologist at The Children’s Hospital of Philadelphia and a Professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania commented in a new release, “Our results show that these engineered “hunter” cells greatly expand in patients, producing very high complete response rates that then persist in patients, potentially allowing for long-term disease control. Our next step is to conduct a Phase II, multi-site trial to assess safety and efficacy in multiple centers, which is now underway.”
Stephan A. Grupp collaborates with Carl H. June, M.D., at the Penn Medicine, who implements this therapy in adult patients with other forms of cancer. The CTL019 therapy previously received a Breakthrough Therapy designation by U.S. Food and Drug Administration earlier this year and Novartis has acquired this therapy’s exclusive rights from Penn back in 2012.
