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Clinical Therapy Trials |
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
3 Address correspondence to David M. Ashley, Department of Hematology and Oncology, Royal Children's Hospital, Flemington Road, Parkville, Victoria, Australia 3052 (david.ashley{at}rch.org.au).
Abstract
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.
References
Ashley, D.M., and Bigner, D.D. (1997) Recent advances in the biology of central nervous system tumors. Curr. Opin. Neurol. 10,445 -451.[ISI][Medline]
Ashley, D.M., Faiola, B., Nair, S., Hale, L.P., Bigner, D.D., and
Gilboa, E. (1997) Bone marrow-generated dendritic cells pulsed
with tumor extracts or tumor RNA induce antitumor immunity against central
nervous system tumors. J. Exp. Med.
186,1177
-1182.
Bergsagel, D.E. (1971) An assessment of massive-dose chemotherapy of malignant disease. Can. Med. Assoc. J. 104, 31-36.[Medline]
Bullard, D.E., Thomas, D.G., Darling, J.L., Wikstrand, C.J., Diengdoh, J.V., Barnard, R.O., Bodmer, J.G., and Bigner, D.D. (1985) A preliminary study utilizing viable HLA mismatched cultured glioma cells as adjuvant therapy for patients with malignant gliomas. Br. J. Cancer 51,283 -289.[ISI][Medline]
Cinque, S., Willems, J., Depraetere, S., Vermeire, L., and Joniau, M. (1992) "In vitro" effect of interleukin-1 beta on human glioma cell lines: Regulation of cell proliferation and IL-6 production. Immunol. Lett. 34,267 -271.[CrossRef][ISI][Medline]
De Vries, I.J., Krooshoop, D.J., Scharenborg, N.M., Lesterhuis,
W.J., Diepstra, J.H., Van Muijen, G.N., Strijk, S.P., Ruers, T.J., Boerman,
O.C., Oyen, W.J., Adema, G.J., Punt, C.J. and Figdor, C.G. (2003)
Effective migration of antigen-pulsed dendritic cells to lymph nodes in
melanoma patients is determined by their maturation state. Cancer
Res. 63,12
-17.
Dhodapkar, M.V., Krasovsky, J., Steinman, R.M., and Bhardwaj, N. (2000) Mature dendritic cells boost functionally superior CD8(+) T-cell in humans without foreign helper epitopes. J. Clin. Invest. 105,R9 -R14.
Geiger, J.D., Hutchinson, R.J., Hohenkirk, L.F., McKenna, E.A., Yanik, G.A., Levine, J.E., Chang, A.E., Braun, T.M., and Mule, J.J. (2001) Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res.,8513 -8519.
Heiser, A., Dahm, P., Yancey, D.R., Maurice, M.A., Boczkowski, D.,
Nair, S.K., Gilboa, E., and Vieweg, J. (2000) Human dendritic
cells transfected with RNA encoding prostate-specific antigen stimulate
prostate-specific CTL responses in vitro. J. Immunol.
164,5508
-5514.
Hosking, C.S., and Balloch, A. (1983) A formula to assess lymphocyte responsiveness in vitro. Birth Defects Orig. Article Ser. 19,21 -23.
Huettner, C., Paulus, W., and Roggendorf, W. (1995) Messenger RNA expression of the immunosuppressive cytokine IL-10 in human gliomas. Am. J. Pathol. 146,317 -322.[Abstract]
Mitchell, A.E., Elder, J.E., Mackey, D.A., Waters, K.D., and Ashley, D.M. (2001) Visual improvement despite radiologically stable disease after treatment with carboplatin in children with progressive low-grade optic/thalamic gliomas. J. Pediatr. Hematol. Oncol. 23,572 -577.[CrossRef][ISI][Medline]
Murphy, J.B., and Sturm, E. (1923) Conditions determining the transplantability of tissues in the brain. J. Exp. Med. 38,183 -197.[Abstract]
NCI. National Cancer Institute, Cancer Therapy Evaluation Program (1999) Common Toxicity Criteria—Version 2.0. Rockville, Md.: NCI Division of Cancer Treatment and Diagnosis (available at http://ctep.cancer.gov/reporting/ctc.html).
Porgador, A., and Gilboa, E. (1995) Bone
marrow-generated dendritic cells pulsed with a class I-restricted peptide are
potent inducers of cytotoxic T lymphocytes. J. Exp.
Med. 182,255
-260.
Romani, N., Reider, D., Heuer, M., Ebner, S., Kampgen, E., Eibl, B., Niedewieser, D., and Schuler, G. (1996) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J. Immunol. Methods 196,137 -151.[CrossRef][ISI][Medline]
Sampson, J.H., Crotty, L.E., Lee, S., Archer, G.E., Ashley, D.M.,
Wikstrand, C.J., Hale, L.P., Small, C., Dranoff, G., Friedman, A.H., Friedman,
H.S., and Bigner, D.D. (2000) Unarmed, tumor-specific monoclonal
antibody effectively treats brain tumors. Proc. Natl. Acad. Sci.
USA 97,7503
-7508.
Shelton, M.S., Meek, F., and Hoskings, C.S. (1974) Serum immunoglobulin levels in children. Aust. J. Med. Technol. 5,113 .
Shirai, Y. (1923) Transplantations of rat sarcomas in adult heterogeneous animals. Jpn. Med. World 1, 14-15.
Simonsen, O., Bentzon, M.W., and Heron, I. (1986) ELISA for the routine determination of antitoxic immunity to tetanus. J. Biol. Stand. 14,231 -239.[CrossRef][ISI][Medline]
Stockwin, L.H., McGonagle, D., Martin, I.G., and Blair, G.E. (2000) Dendritic cells: Immunological sentinels with a central role in health and disease. Immunol. Cell Biol. 78, 91-102.[CrossRef][Medline]
Tada, M., and de Tribolet, N. (1993) Recent advances in immunobiology of brain tumors. J. Neurooncol. 17,261 -271.[CrossRef][Medline]
Yu, J.S., Wheeler, C.J., Zeltzer, P.M., Ying, H., Finger, D.N.,
Lee, P.K., Yong, W.H., Incardona, F., Thompson, R.C., Riedinger, M.S., Zhang,
W., Prins, R.M., and Black, K.L. (2001) Vaccination of malignant
glioma patients with peptide-pulsed dendritic cells elicits systemic
cytotoxicity and intracranial T-cell infiltration. Cancer
Res. 61,842
-847.
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