Sepsis as innate immune stimulus: severe sepsis exposures and protection against relapse in children with acute leukemias
Children who continue to have small amounts of leukemia after chemotherapy, known as minimal residual disease (MRD), have a high risk of relapse. Since these MRD cells survived through chemotherapy, giving additional standard chemotherapy is not effective and new treatments are urgently needed.
Some leukemia cells carry a specific feature called an "antigen." Researchers have developed ways to allow immune cells called T-cells to recognize the antigen and kill the leukemia. These treatments are extremely successful, but one in three children relapses afterwards. In addition, some children have leukemia without unique antigens and thus no immune therapy options.
We study drugs that stimulate the immune system similarly to a bacterial or viral infection. This stimulation causes immune cells to recognize and kill leukemia and does not require a specific antigen. Mice cured using this drug have "immune memory" allowing them to reject new leukemia cells, similar to the body rejecting an infection after a vaccine.
Some children receiving therapy for leukemia unfortunately develop serious infections. However, we can learn from these children by studying whether they have similar responses to mice who receive immune system-stimulating drugs. We collected information from a large group of children with leukemia from across the U.S. We will study whether children who develop severe infections are less likely to relapse than children without infections, focusing on those with MRD. This would support developing clinical trials of immune stimulating drugs and may offer new options to children who currently have no available immune therapy.
"My very first grant was a Young Investigator Award from Alex’s Lemonade Stand Foundation. At the time, we were studying a drug that stimulated the immune system like a bacterial or viral infection would, which then triggered immune cells to be on “high alert” for leukemia cells. This treatment worked very well in the lab and is currently in early clinical trials. We know that this non-specific stimulation of the immune system is very similar to what happens when kids get severe infections, and we realized we could study this treatment on a much larger scale than what would be possible to do in an early clinical trial by looking at whether children who happened to have bad infections during treatment for leukemia were less likely to experience relapses than children who did not have severe infections.
This project is taking the work we did with the support of that very first grant from ALSF and expanding it to a national level! To receive a grant from the Alex’s Lemonade Stand Foundation is a tremendous honor – the impact that Alex and her parents have had on childhood cancer research and supporting patients and families is truly heroic. I am immeasurably grateful for their efforts in supporting my work and that of countless other scientists fighting to find a cure." -Alix Seif