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Results of a phase I study utilizing monocyte‐derived dendritic cells pulsed with tumor RNA in children with stage 4 neuroblastoma
Author(s) -
Caruso Denise A.,
Orme Lisa M.,
Amor Gerlinda M.,
Neale Alana M.,
Radcliff Fiona J.,
Downie Peter,
Tang Mimi L. K.,
Ashley David M.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20911
Subject(s) - medicine , neuroblastoma , immune system , cd8 , immunology , antigen , dendritic cell , cd80 , population , cancer research , cytotoxic t cell , biology , cd40 , cell culture , biochemistry , genetics , environmental health , in vitro
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. Cancer 2005. © 2005 American Cancer Society.