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. We recently reviewed approaches under pre-clinical development as well as those making their way into clinical trials. (R. Nguyen and C.J. Thiele, Immunotherapy approaches targeting neuroblastoma. Curr. Opin. Hematol. Oncol., 2021). Complex model systems that recapitulate the tumor microenvironment are important components to evaluate therapies as studies near translation to the clinic. We 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. Ongoing correlative studies are documenting efficacy of treatments and assessments of tissue and bone metastasis after CAR T therapy as well as CAR T persistence and extent of exhaustion. Current studies are examining the modifications to the CT3 CAR to enhance efficacy and in vivo persistence.