© 2004 by Society
© 2004 by the Society forNeuro-Oncology
Results of a phase 1 study utilizing monocyte-derived dendritic cellspulsed with tumor RNA in children and young adults with brain cancer
Departments of Hematology and Oncology (D.A.C, L.M.O.,A.M.N., F.J.R., G.M.A., P.D., D.M.A.), Neurosurgery(W.M.), and Immunology (M.L.K.T.), The RoyalChildren's Hospital, Parkville, Victoria, 3051; Department of Hematology and Oncology, The Royal Children'sHospital, Brisbane, Queensland, 4029 (T.E.H.); Department of Pediatrics (D.A.C., D.M.A.), The Universityof Melbourne, Parkville, Victoria, 3052; The MurdochChildrens Research Institute (D.A.C., A.M.N., G.M.A., T.E.H., M.L.K.T.,D.M.A.), Parkville, Victoria, 3052; Australia
3 Address correspondence to David M. Ashley, Department of Hematology andOncology, Royal Children's Hospital, Flemington Road, Parkville, Victoria,Australia 3052(david.ashley{at}rch.org.au).
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Abstract |
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We conducted a phase 1 study of 9 pediatric patients with recurrent braintumors using monocyte-derived dendritic cells pulsed with tumor RNA to produceantitumor vaccine (DCRNA) preparations. The objectives of thisstudy included (1) establishing safety and feasibility and (2) measuringchanges in general, antigen-specific, and tumor-specific immune responsesafter DCRNA. Dendritic cells were derived from freshly isolatedmonocytes after 7 days of culture with IL-4 and granulocyte-macrophagecolony-stimulating factor, pulsed with autologous tumor RNA, and thencryopreserved. Patients received at least 3 vaccines, each consisting of anintravenous and an intradermal administration at biweekly intervals. The studyshowed that this method for producing and administering DCRNA froma single leukapheresis product was both feasible and safe in this pediatricbrain tumor population. Immune function at the time of enrollment into thestudy was impaired in all patients tested. While humoral responses to recallantigens (diphtheria and tetanus) were intact in all patients, cellularresponses to mitogen and recall antigens were below normal. FollowingDCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1of 7 showed a partial response. Two of 7 patients who were tested showed atumor-specific immune response to DCRNA. This study showed thatDCRNA vaccines are both safe and feasible in children with tumorsof the central nervous system with a single leukapheresis.
Received November 12, 2003; Accepted January 23, 2004
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