Burdach et al. (Abstract)
Cellular Therapy and Transplantation (CTT), Vol. 3, No. 9
doi: 10.3205/ctt-2010-No9-abstract46
© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported
Abstract accepted for "4th Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation",
Saint Petersburg, Russia, September 18–20, 2010
Frontiers of cellular therapy in childhood cancer: overcoming tumor escape by selective alloreactive T cells
Stefan Burdach, Uwe Thiel, Günther H.S. 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, Technische Universität München, 81664 Munich, Germany, E-mail: stefan.burdach@lrz.tum.de
Abstract
Pediatric malignancies are characterized by an early systemic spread. The escalation of cytotoxic therapies necessitating stem cell rescue has yielded definitive but finite increments in cure (e.g. 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. We evaluated allorestricted CD8+ T cells against Ewing Tumor (ET) antigens identified by microarrays. Following peptide stimulations with HLA-A*0201+ dendritic cells (DC), allorestricted HLA-A*0201- CD8+ T cells were sorted with HLAA* 0201/peptide pentamers and expanded by limiting dilution. Expanded T cells specifically recognized target or antigen transfected cells in the context of HLAA* 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. Immunization with peptide loaded DC induced an allorestricted T cell response, suppressing tumor growth. Results indicate that defined ET selective peptides are capable of eliciting a protective allorestricted CD8+ T cell response against a non-immunogenic pediatric solid tumor in vivo. Thus, alloreactive tumor- selective T cells may complement haploidentical stem cell transplants in solid tumors of childhood and adolescence.
Keywords: childhood cancer, immunotherapy, alloreactive T cells
