David Teachey Laboratory
Led by David T. Teachey, MD, researchers in the Teachey Laboratory are focused studying perturbations in leukemic cell signal transduction pathways. Their goal is to identify targeted cancer inhibitors and immunotherapies that can treat children with high-risk leukemias and autoimmune lymphoproliferative syndrome (ALPS). The long-term goal of the research conducted in this laboratory is to develop better therapies, improve cure rates and minimize toxicities for children with high-risk leukemias and ALPS.
Ongoing studies in the Teachey laboratory demonstrated that children with high-risk leukemias, such as Philadelphia chromosome-like lymphoblastic leukemia (Ph-like ALL) and early T-cell precursor acute lymphoblastic leukemia (T-ALL), have dysregulated cell signaling in the MAPK/JAK/STAT and PI3K/mTOR pathways. The targeted JAK kinase inhibitor ruxolitinib was found to be highly active in slowing disease progression in Ph-like ALL and ETP-ALL animal models.
Based on these findings, researchers in the Teachey laboratory are participating in a Phase II clinical trial to evaluate the effectiveness of ruxolitinib as a treatment for children with high-risk ALL that are characterized by dysregulated JAK/STAT signaling mutations.
Other studies in the Teachey Laboratory found that PI3K/AKT/mTOR protein kinase signaling is dysregulated in children with ALPS. The targeted mTOR kinase inhibitor sirolimus (rapamycin) was found to inhibit disease progression in mouse xenograft models of ALPS. Pilot clinical studies with pediatric ALPS patients revealed that sirolimus treatment resulted in a complete and durable response (with minimal toxicity) to over 90 percent of the trial participants.
Additional clinical studies are planned to evaluate the safety and effectiveness of sirolimus as a treatment for children with refractory pediatric autoimmune diseases.
Researchers in the Teachey Laboratory are also focused on elucidating the underlying molecular mechanisms that contribute to development of cytokine release syndrome (CRS). CRS occurs in some children with ALL who are treated with chimeric antigen receptor T cells (CART) or bispecific T-cell engaging (BiTE) antibody immunotherapy. Clinical studies have revealed that that administration of tocilizumab — a humanized anti-IL6 receptor monoclonal antibody that interferes with secretion of the cytokine IL6 — can effectively treat pediatric patients who develop CRS after CART or BiTE immunotherapy. Studies are underway to gain a better understanding of the role of IL6 in CRS and to identify genetic markers that may help to identify children who may be at high risk of developing CRS during CART or BiTE immunotherapy.
Future studies in the Teachey Laboratory will continue to focus on identification and clinical evaluation of novel immunotherapies and targeted cancer inhibitors to treat children with high-risk leukemias and ALPS.