Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer.
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.
Dohnal
A M
AM
Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria.
Witt
V
V
Hügel
H
H
Holter
W
W
Gadner
H
H
Felzmann
T
T
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
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin