T cell-based immunotherapy approaches for neuroblastoma
Session type: Parallel sessions
Despite combination treatment approaches including surgery, radiotherapy and myeloablative chemotherapy, most children with high-risk neuroblastoma succumb to their disease. Survivors have considerable long-term morbidity due to intensive treatment. New treatment strategies are badly needed.
Chimeric antigen receptors (CARs) consist of the antigen recognising domain of an antibody linked to intracellular portions of T cell signalling receptors. Using retroviral vectors patient T cells can be engineered to express tumour-specific CARs. These CAR-engineered T-cells can penetrate a solid core of tumour, release inflammatory cytokines, lyse tumour cells, proliferate at sites of disease and persist in vivo for years.
Disialoganglioside GD2 provides an attractive target antigen for CAR T cell therapy: GD2 is expressed in virtually all neuroblastomas regardless of stage or site of disease while expression on normal tissue is limited. There is extensive experience targeting this antigen with monoclonal antibodies. In addition, adoptive T cell immunotherapy with a GD2-specific CAR has shown promise in a phase I study in refractory/relapsed neuroblastoma.
Since this phase I study, CAR design, vector technology and insight in optimal immunotherapy treatment regimens has evolved. Recently, with next generation CARs and combination with lymphodepletion, CD19-CAR T cell therapy has led to unprecedented responses in patients with chemotherapy resistant leukaemias.
Our preclinical and translational work of the next generation GD2-CAR T cell therapy study will be presented as well as strategies to further refine the specificity and improve the efficacy of this immunotherapy approach.