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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2046-2054.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-07-2379.
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GENE THERAPY
RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy
Christina M. Coughlin,
Barbara A. Vance,
Stephan A. Grupp, and
Robert H. Vonderheide
From the Divisions of Hematology and Oncology, Children's Hospital of Philadelphia, and the Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia.
Vaccination with antigen-presenting cells (APCs) engineered to mimic mechanisms of immune stimulation represents a promising approach for cancer immunotherapy. Dendritic cell vaccines have entered phase 3 testing in adult malignancies, but such vaccines in children have been limited. We demonstrate that CD40-activated B cells (CD40-B) transfected with RNA may serve as an alternative vaccine that can be generated from small blood volumes regardless of patient age. CD40-B from pediatric patients are efficient APCs and can be loaded with RNA as an antigenic payload, permitting simultaneous targeting of multiple antigenic epitopes without the necessity of HLA matching. For viral and tumor antigens, CD40-B/RNA technology induced cytotoxic T lymphocytes (CTLs) from adults and children, which could be identified with peptide/major histocompatibility complex (MHC) tetramers. These CTLs secreted interferon- (IFN-) and killed targets in an MHC-restricted fashion. For pooled neuroblastoma RNA and autologous neuroblastoma RNA, CTLs that lysed neuroblastoma cell lines, including CTLs specific against the widely expressed tumor-antigen survivin, were generated. These findings support a novel platform for tumor-specific vaccine or adoptive immunotherapies in pediatric malignancies.
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