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Keywords:

  • vaccine;
  • neuroblastoma;
  • immunocompetency;
  • immunotherapy

Abstract

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 (DCRNA).

METHODS

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

RESULTS

The results showed that this method for producing and administering DCRNA 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 DCRNA 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 DCRNA. Among the patients who had measurable disease at the time of DCRNA vaccine, none showed any objective tumor response.

CONCLUSIONS

DCRNA 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. Cancer 2005. © 2005 American Cancer Society.