RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy.
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-gamma (IFN-gamma) 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.
Coughlin
Christina M
CM
Division of Hematology and Oncology, Children's Hospital of Philadelphia, and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 19104, USA.
Vance
Barbara A
BA
Grupp
Stephan A
SA
Vonderheide
Robert H
RH
D000328:Adult; D000367:Age Factors; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics*; D019496:Cancer Vaccines; D002648:Child; D018274:Electroporation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D066298:In Vitro Techniques; D007251:Influenza, Human / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D019013:CD40 Antigens; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D012333:RNA, Messenger