Stephan Grupp Laboratory
Led by Stephan Grupp MD, PhD, researchers in the Grupp Laboratory are focused on developing new molecular-based targeted cancer treatments and cell-based immunotherapies to treat leukemia and solid tumors. The ultimate goal of the work conducted in this laboratory is to identify and develop advanced cancer treatments that are less toxic than existing therapies and can be used to treat children with high-risk malignancies.
Previous studies in the Grupp Laboratory that focused on the genetics and unique characteristics of pediatric neuroblastomas led to the development of a pioneering treatment for high-risk neuroblastoma called tandem treatment. This treatment consists of sequential courses of high-dose chemotherapy coupled with stem cell transplants given six weeks apart. A nationalized randomized Phase III clinical trial has been completed to determine if the tandem transplant protocol will replace the existing standard of care for high-risk pediatric neuroblastomas.
Ongoing studies in the Grupp Laboratory are evaluating the use of chimeric antigen receptor (CAR) T cell immunotherapy to treat children with high-risk acute lymphoblastic leukemia (ALL). Results from a pilot clinical study demonstrated that treatment of children or adults with treatment refractory or relapsed ALL with CART19 cells (CD19) resulted in complete remission rates of 90 percent and durable remission for up to 24 months.
Because a subset of ALL patients treated with CART19 relapsed and developed CD19 negative leukemias, a new pilot study was initiated to evaluate CART22 as an immunotherapy for children who relapse after CART19 treatment and developed CD19-negative leukemias. Currently, an open-label Phase 1A/II clinical trial is underway to evaluate CART19 as treatment for children with chemotherapy resistant or refractory CD19+leukemia and lymphoma.
Additional studies in the Grupp Laboratory are investigating CART cells directed against the tumor-associated disialoganglioside GD2 as a treatment for neuroblastoma and other solid tumors. Results from studies with mouse xenograft models of neuroblastoma showed that RNA-modified GD2 CART cells induced antitumor responses and were able to control disseminated neuroblastoma disease.
Other studies in the Grupp Laboratory showed that the JAK inhibitor ruxolitinib and the P13K/mTOR inhibitor sirolimus inhibited cell signal transduction and substantially reduced leukemic disease burden in JAK/STAT or P13K/mTOR mouse xenograft models of ALL. A phase I clinical trial is currently being planned to evaluate combinations of ruxolitinib or sirolimus with standard chemotherapy to treat high-risk pediatric ALL with dysregulated JAK/STAT and P13K/mTOR
Future studies in the Grupp Laboratory will continue to focus on refining CART immunotherapy as a treatment for high-risk pediatric leukemias and neuroblastomas and the clinical development of new targeted cancer therapies to treat children with high-risk or treatment refractory/relapsed ALL.