Results of a phase I study utilizing monocyte‐derived dendritic cells pulsed with tumor RNA in children with stage 4 neuroblastoma

• Published in: Cancer 2005-03, Vol.103 (6), p.1280-1291
• Main Authors: Caruso, Denise A., Orme, Lisa M., Amor, Gerlinda M., Neale, Alana M., Radcliff, Fiona J., Downie, Peter, Tang, Mimi L. K., Ashley, David M.
• Format: Article
• Language: English
• Subjects: Adrenal Gland Neoplasms - immunology; Adrenal Gland Neoplasms - mortality; Adrenal Gland Neoplasms - pathology; Adrenal Gland Neoplasms - therapy; Biological and medical sciences; Cancer Vaccines - therapeutic use; Child; Child, Preschool; Dendritic Cells - immunology; Female; Humans; immunocompetency; immunotherapy; Immunotherapy - methods; Leukapheresis - methods; Male; Medical sciences; Neoplasm Staging; neuroblastoma; Neuroblastoma - immunology; Neuroblastoma - mortality; Neuroblastoma - pathology; Neuroblastoma - therapy; Neurology; Probability; Retroperitoneal Neoplasms - immunology; Retroperitoneal Neoplasms - mortality; Retroperitoneal Neoplasms - pathology; Retroperitoneal Neoplasms - therapy; Risk Assessment; RNA, Neoplasm - immunology; Sensitivity and Specificity; Survival Analysis; Treatment Outcome; Tumors; Tumors of the nervous system. Phacomatoses; vaccine
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20911

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. An antitumor dendritic cell vaccine that used tumor RNA as the antigen source was both safe and feasible in children with Stage 4 neuroblastoma. Children with neuroblastoma were immunosuppressed profoundly, even though they received lymphocyte‐sparing chemotherapy and had normal numbers of lymphocytes 6 weeks after they finished chemotherapy.