title: Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer.
abstract: BACKGROUND
  Cancer vaccines employing DC in their capacity as APC have been tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response.
  
  
  METHODS
  We applied tumor cell lysate plus keyhole limpet hemocyanin (KLH)-loaded and 48-h lipopolysaccharide (LPS) plus IFN-gamma-stimulated fully mature DC, which do not release IL-12, subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm) DC, which are potent producers of IL-12, subcutaneously (n=6) or intranodally (n=8) as a cancer vaccine to patients suffering from advanced solid pediatric malignancies.
  
  
  RESULTS
  No serious adverse events were observed following application of IL-12-releasing smDC. Following immunization the majority of patients responded positively to KLH in a delayed-type hypersensitivity (DTH) test. In addition, three of six intranodally treated patients responded to the tumor Ag in the DTH test.
  
  
  CONCLUSIONS
  We conclude that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in pediatric cancer patients.
authors.affiliation: Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria.
authors.forename: A M
authors.initials: AM
authors.lastname: Dohnal
authors.forename: V
authors.initials: V
authors.lastname: Witt
authors.forename: H
authors.initials: H
authors.lastname: Hügel
authors.forename: W
authors.initials: W
authors.lastname: Holter
authors.forename: H
authors.initials: H
authors.lastname: Gadner
authors.forename: T
authors.initials: T
authors.lastname: Felzmann
mesh_terms: D000293:Adolescent; D000328:Adult; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002454:Cell Differentiation; D002648:Child; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007272:Injections, Intralymphatic; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin