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Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed
with tumor RNA in children and young adults with brain cancer
Denise A. Caruso, Lisa M. Orme, Alana M. Neale, Fiona J. Radcliff, Gerlinda
M. Amor, Wirginia Maixner, Peter Downie, Timothy E. Hassall, Mimi L.K. Tang,
David M. Ashley
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 Royal Children’s Hospital, Parkville, Victoria, 3051; Department of
Hematology and Oncology, The Royal Children’s Hospital, Brisbane, Queensland,
4029 (T.E.H.); Department of Pediatrics (D.A.C., D.M.A.), The University of
Melbourne, Parkville, Victoria, 3052; The Murdoch Childrens 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
We conducted a phase 1 study of 9 pediatric patients with recurrent brain
tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce
antitumor vaccine (DCRNA) preparations.
The objectives of this study included (1) establishing safety and feasibility
and (2) measuring changes in general, antigen-specific, and tumor-specific
immune responses after DCRNA.
Dendritic cells were derived from freshly isolated monocytes after 7 days of
culture with IL-4 and granulocyte-macrophage colony- stimulating factor, pulsed
with autologous tumor RNA, and then cryopreserved.
Patients received at least 3 vaccines, each consisting of an intravenous and an
intradermal administration at biweekly intervals.
The study showed that this method for producing and administering DCRNA
from a single leukapheresis product was both feasible and safe in this pediatric
brain tumor population.
Immune function at the time of enrollment into the study was impaired in all
patients tested.
While humoral responses to recall antigens (diphtheria and tetanus) were intact
in all patients, cellular responses to mitogen and recall antigens were below
normal.
Following DCRNA vaccine, 2 of 7 patients showed stable clinical
disease and 1 of 7 showed a partial response.
Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA.
This study showed that DCRNA vaccines are both safe and feasible in
children with tumors of the central nervous system with a single leukapheresis.
© 2004 Duke University Press
Source: http://iris.ingentaselect.com/vl=1594156/cl=69/nw=1/rpsv/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n3/s7/p236
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