Accession Number : ADA612327


Title :   Improve T Cell Therapy in Neuroblastoma


Descriptive Note : Annual rept. 1 Jul 2013-30 Jun 2014


Corporate Author : BAYLOR COLL OF MEDICINE HOUSTON TX


Personal Author(s) : Dotti, Gianpietro


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a612327.pdf


Report Date : Jul 2014


Pagination or Media Count : 68


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(alpha) 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 , *T LYMPHOCYTES , ANTIGENS , CELLS(BIOLOGY) , EPSTEIN BARR VIRUS , IMMUNOTHERAPY , NEOPLASMS , RECEPTOR SITES(PHYSIOLOGY)


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE