Childhood cancers are rare, and most of the cancers limited to childhood are profoundly different than the carcinomas that make up the bulk of adult cancers. As such, their origins are likely different and the way in which the immune system must control and interact with them are different.
The Barrett Laboratory was initially focused on developing chimeric antigen receptor therapy (CART) for childhood leukemia, and in the process the lab team noted variation in the T cell proliferative capacity of some patients with lymphomas as compared to leukemias. The team extended this investigation into all childhood cancers, and found various, yet subtle, T cell deficiencies at diagnosis in most pediatric solid tumor patients. The Barrett lab currently strives to understand if these deficits are induced by the tumor or are pre-existing. In addition, the lab works to develop immune-based therapies – including CART and immune checkpoint inhibitors – and rationally integrate them into current standards of care.
- Effects of chemotherapy on T cell function: Most immune-based therapies are given after children have received chemotherapy. The Barrett Lab wishes to understand the effects of each chemo regimen on T cell function to better design and deliver immune based therapies.
- Adaptive manufacturing of CAR T cells: CAR T cells are incredibly effective at inducing remission in patients with CD19 positive malignancies. Pre-clinical testing, however, has failed to reveal the reasons why some patients will have T cell that last years while others only days. The lab is investigating predictive biomarkers of successful T cell persistence and devise strategies to convert poor persisting T cell therapies to long lasting ones.
- Cytokine Release syndrome: One of the toxic side effects of CART is a poorly understood cytokine release syndrome that can be life threatening. The lab strives to uncover the triggering mechanisms for this toxicity and devise strategies to mitigate it.
- Immune function of children with cancer: Research in the lab has described subtle yet persistent changes in T cell function depending on cancer type that exist prior to chemotherapy. The team seeks to uncover the effects of the tumor on peripheral blood T cells as well as any pre-existing deficits that may have allowed tumor formation.
- Lymphatic Fluid analysis: T cells exist in more than just peripheral blood. In collaboration with specialists in lymphatic malformations, the Barrett Lab is studying the phenotype and function of T cells from lymphatic fluid versus peripheral blood in order to better understand T cell biology and potentially exploit these differences for more effective immune therapies.
Dr. Barret's research program focuses on immune function of children with cancer. His research involves investigating possible immune deficiencies that result in children developing cancer and developing immune-based therapies for childhood cancer.