[English]  [Pусский]  [中文]  
 
ctt-journal > Burdach et al. (Abstract)

Burdach et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract93

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

Preliminary Program

Contribute a comment

Target identification and cellular engineering in childhood cancer immunotherapy

Stefan Burdach, Uwe Thiel and Günther HS Richter

Laboratory for Functional Genomics and Transplantation Biology, Department of Pediatrics, Children’s Cancer Research Center and Roman Herzog Comprehensive Cancer Center, Technische Universität München, Munich, Germany

Correspondence: Stefan Burdach, Laboratory for Functional Genomics and Transplantation Biology, Department of Pediatrics, Children’s Cancer Research Center and Roman Herzog Comprehensive Cancer Center, Technische Universität München, 81664 Munich, Germany, E-mail: stefan.burdach@spam is badlrz.tum.de

Abstract

Treatment of pediatric malignancies is associated with high toxicity. In addition, these malignancies are characterized by early systemic spread. Escalation of cytotoxic therapies necessitating stem cell rescue has yielded finite increments in cure rates recently (Burdach et al. 2010). Effective immunotherapy of these malignancies is hampered by an ineffective T-cell repertoire against tumor antigens and the inability of the host immune system to overcome tolerance-inducing mechanisms. In mice and humans we evaluated allorestricted CD8+ T-cells against novel Ewing Tumor (ET) antigens previously identified by microarrays in vivo. Following peptide stimulations with HLA-A*0201+ dendritic cells (DC), allorestricted HLA-A*0201- CD8+ T-cells were sorted with HLA-A*0201/peptide pentamers and expanded by limiting dilution. Culture conditions were engineered to retain a central memory (CM) phenotype. Expanded T-cells specifically recognized target or antigen transfected cells in the context of HLA-A*0201 and specifically killed HLA-A*0201+ ET cells expressing the antigen. Immunizing humanized Rag2-/-gC-/- mice suppressed tumor growth and specific allorestricted CD8+ T-cells were re-isolated. We established allorestricted cytotoxic T-cell lines specifically directed against HLA-A*0201-restricted ET peptides and cloned the TCR to generated transgenic ET-specific T-cells. Infusion of ET-selective allorestricted CM CD8+ T-cells in vivo was not associated with any side effects, and in particular no GVHD was observed. Thus, alloreactive tumor-selective T-cells may complement haploidentical stem cell transplants in solid tumors of childhood and adolescence.

Keywords:
childhood cancer, immunotherapy, target, alloreactive T-cells