Accession Number : ADA610046


Title :   Improve T Cell Therapy in Neuroblastoma


Descriptive Note : Annual rept. 1 Jul 2011-30 Jun 2012


Corporate Author : BAYLOR COLL OF MEDICINE HOUSTON TX


Personal Author(s) : Dotti, Gianpietro


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a610046.pdf


Report Date : Jul 2012


Pagination or Media Count : 39


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 :   *IMMUNITY , *MONOCLONAL ANTIBODIES , *NEUROBLASTOMA , *T LYMPHOCYTES , CELLS(BIOLOGY) , HOMEOSTASIS , IN VITRO ANALYSIS , IN VIVO ANALYSIS , NEOPLASMS , NEUROBLASTS , RESPONSE(BIOLOGY) , SURGICAL TRANSPLANTATION , VACCINES


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE