Maude Laboratory Research Overview

In partnership with the University of Pennsylvania and Novartis, researchers in the Center for Childhood Cancer Research are developing and evaluating chimeric antigen receptor (CAR) T cells to treat children with relapsed/refractory acute lymphoblastic leukemia (ALL).

T cells can be engineered to target specific antigens on the surface of leukemic cells. After infusion into patients, CAR T cells bind to tumor target antigens, which induces an immune effector cell cytotoxic response that kills malignant cancer cells.

Remission rates exceeding 90% have been seen in a phase I/IIa trial of CAR T cells targeting CD19, but some patients relapse. To overcome one type of relapse, a phase 1 trial, led by Dr. Maude, is underway to evaluate the safety and efficacy of humanized CAR T cells targeting CD19 (CART19) as a treatment for pediatric patients with chemotherapy resistant or refractory CD19+ ALL and lymphoma.

ALL is the most common childhood cancer. Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) and early T-cell precursor ALL (ETP-ALL) are high-risk subtypes of ALL that are characterized by aggressive disease progression and poor prognosis.

Using animal-based xenograft models of ALL, researchers found that both Ph-like ALL and ETP-ALL have dysregulated cell signaling in MAPK, JAK/STAT and PI3K/AKT/mTOR pathways.

Additional studies revealed that a JAK inhibitor called ruxolitinib was highly active in slowing disease progression in both Ph-like-ALL and ETP-ALL disease models. Ruxolitinib is a targeted cancer therapy that has previously been approved to treat adult myeloproliferative diseases.

Early-stage clinical trials in partnership with the Children’s Oncology Group are being developed to evaluate the efficacy and safety of a combination of ruxolitinib with standard chemotherapy to treat high-risk ALL with dysregulated JAK/STAT signaling mutations.

Other studies are currently underway to identify novel targeted cancer therapies that can be used to safely and effectively treat high-risk subsets of pediatric ALL.