Improve T Cell Therapy in Neuroblastoma
Technical Report,01 Jul 2010,30 Jun 2015
Baylor College of Medicine Houston United States
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Neuroblastoma NB is the most common malignant extracranial tumor of childhood. Since NB appears susceptible to immunotherapies that include monoclonal antibodies and T-cell immune responses elicited by tumor vaccine, we have combined the beneficial effects of both humoral and cell-mediated components of the anti tumor response. We demonstrated indeed that adoptive transfer of Epstein-Barr-virus EBV-specific cytotoxic T lymphocytes EBV-CTLs genetically modified to express a chimeric antigen receptor CAR-GD2 targeting the GD2 antigen expressed by neuroblasts persist in the peripheral blood and induce objective tumor responses including complete remissions. We will now augment the expansion and survival of CAR-GD2 modified EBV-CTLs by coexpressing the IL-7R that restores their capacity to respond to homeostatic IL-7. We will also enhance the capacity of these cells to invade solid tumor masses by expressing heparanase HPSE that disrupts the non-cellular stromal elements of NB. Experiments will be conducted in vitro and in vivo in a xenograft mouse model.