Neuroblastoma Tumor Microenvironment: tumor growth and immune regulation

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Targeting solid tumors is the next challenge for developing effective immuno-oncological approaches. Complex model systems that recapitulate the tumor microenvironment are important components to evaluate therapies as studies near translation to the clinic. In relation to Specific Aim 1 we have developed a "Bar-coded" neuroblastoma patient derived xenograft tumor to enable studies to track at the single cell level to growth and evolution of NB tumor cells under different therapeutic pressures. recently initiated studies of a CART targeting GPC2(CT3-8BB) a protein highly expressed in Neuroblastoma tumor cells using our orthotopic, spontaneous metastasis NB model. Results of these studies indicated that the CT3-8BB CAR T cells regress neuroblastoma tumors in both an experimental metastasis NB model as well as orthotopic NB model with spontaneous metastases (N. Li et al, Cell Rep. Med. 2021) using cell lines as well as patient derived xenografts. Recent studies document the efficacy of treatments and assessments of tissue and bone metastasis after CAR T therapy as well as CAR T persistence and extent of exhaustion. In a publication Sun et al J. Immunother Cancer 2023 we evaluated and identified through iterative pre-clinical engineering and evaluation in pre-clinical models of neuroblastoma the best CAR T to move into production for clinical trials in pediatric patients with neuroblastoma.