Neuroblastoma Tumor Microenvironment: tumor growth and immune regulation

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

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. Anti-GD2 therapy is used in the treatment of High-Risk Neuroblastoma. Immunocytokines, antibodies conjugated with cytokines, have been postulated to have better activity than antibodies alone. Currently a phase 2 clinical trial is underway with anti-GD2 antibody conjugated with IL-2. In a recent collaborative study we have compared in syngeneic and xenograft models of Neuroblastoma anti-GD2 conjugated to different members of the gamma cytokine family and identified superior candidates with better efficacy (Nguyen et al Clin. Cancer Res. 2022)