Results of a Phase I study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children with Stage 4 neuroblastoma.
BACKGROUND
A Phase I study of 11 pediatric patients with newly diagnosed, Stage 4 neuroblastoma was conducted using monocyte-derived dendritic cells (DC) pulsed with tumor RNA to produce antitumor vaccines (DC(RNA)).


METHODS
Patients received two courses of induction with carboplatin followed by standard chemotherapy, surgery, radiation, high-dose therapy, stem cell rescue, and DC(RNA) vaccine therapy.


RESULTS
The results showed that this method for producing and administering DC(RNA) from a single leukapheresis product was both feasible and safe in this pediatric neuroblastoma population. Two courses of carboplatin maintained lymphocyte counts at normal levels. However, immune function 6 weeks after high-dose chemotherapy and stem cell rescue and prior to receiving DC(RNA) was impaired in all patients tested. There was an alteration in the ratio of CD4-positive and CD80-positive T cells. CD4-positive cell numbers were below normal, whereas CD8-positive cell numbers were above normal for all patients. In addition, CD19-positive cell numbers were below normal for all but one patient. It was found that humoral responses to recall antigens (diphtheria and tetanus) and cellular responses to mitogen and recall antigens were below normal in most patients. Despite this, two of three patients tested showed a tumor-specific humoral immune response to DC(RNA). Among the patients who had measurable disease at the time of DC(RNA) vaccine, none showed any objective tumor response.


CONCLUSIONS
DC(RNA) vaccines were both safe and feasible in children with Stage 4 neuroblastoma. Humoral responses to tumor were detected, although remained immunosuppressed at the time of administration, limiting efficacy.
Caruso
Denise A
DA
Department of Hematology and Oncology, The Royal Children's Hospital, Parkville, Victoria, Australia.
Orme
Lisa M
LM
Amor
Gerlinda M
GM
Neale
Alana M
AM
Radcliff
Fiona J
FJ
Downie
Peter
P
Tang
Mimi L K
ML
Ashley
David M
DM
D000310:Adrenal Gland Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007937:Leukapheresis / Q000379:methods; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D011336:Probability; D012334:RNA, Neoplasm / Q000276:immunology*; D012186:Retroperitoneal Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
D019496:Cancer Vaccines; D012334:RNA, Neoplasm