Accession Number : AD1011375


Title :   Improve T Cell Therapy in Neuroblastoma


Descriptive Note : Technical Report,01 Jul 2010,30 Jun 2015


Corporate Author : Baylor College of Medicine Houston United States


Personal Author(s) : Gianpietro,Dotti


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1011375.pdf


Report Date : 01 Sep 2015


Pagination or Media Count : 30


Abstract : 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.


Descriptors :   neuroblastoma , immunotherapy , neoplasms , in vitro analysis , in vivo analysis , mice , cells(biology)


Distribution Statement : APPROVED FOR PUBLIC RELEASE