Adjuvant Dendritic Cell-Based Tumour Vaccination for Children With Malignant Brain Tumours

被引:99
作者
Ardon, Hilko [1 ,2 ]
De Vleeschouwer, Steven [1 ,2 ]
Van Calenbergh, Frank [1 ]
Claes, Laurence [3 ]
Kramm, Christof M. [4 ]
Rutkowski, Stefan [5 ]
Wolff, Johannes E. A. [6 ]
Van Gool, Stefaan W. [2 ,7 ]
机构
[1] Univ Hosp Gasthuisberg, Dept Neurosurg, B-3000 Louvain, Belgium
[2] Univ Hosp Gasthuisberg, Expt Immunol Lab, B-3000 Louvain, Belgium
[3] Catholic Univ Louvain, Dept Psychol, B-3000 Louvain, Belgium
[4] Univ Childrens Hosp, Dept Paediat Oncol Haematol & Immunol, Halle, Germany
[5] Univ Med Ctr Hamburg Eppendorf, Dept Paediat Haematol & Oncol, Hamburg, Germany
[6] Univ Texas MD Anderson Canc Ctr, Dept Paediat Oncol, Houston, TX 77030 USA
[7] Univ Hosp Gasthuisberg, Dept Paediat, B-3000 Louvain, Belgium
关键词
brain tumours; dendritic cell vaccination; immunotherapy; CENTRAL-NERVOUS-SYSTEM; ATYPICAL TERATOID/RHABDOID TUMOR; HIGH-DOSE THIOTEPA; HIGH-GRADE GLIOMA; PHASE-I/II TRIAL; GLIOBLASTOMA-MULTIFORME; COMBINATION THERAPY; RECURRENT GLIOMA; ORAL ETOPOSIDE; YOUNG-ADULTS;
D O I
10.1002/pbc.22319
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background. A large experience with dendritic cell (DC)-based vaccination for malignant brain tumours has been gained in adults Here we focus on the results obtained in children with relapsed malignant brain tumours Procedure. In total 45 children were vaccinated 33 high grade glioma (HGG), 5 medulloblastoma (MB)/primitive neuro-ectodermal tumour (PNET), 4 ependymoma and 3 atypical teratoid-rhabdoid tumour (ATRT) Autologous, monocyte-derived DC were generated and loaded with tumour lysate, which was used as source of tumour-associated antigens Results. In 38 patients peripheral blood mononuclear cells (PBMC) were obtained from leukapheresis and in 7 patients from fresh blood samples 7 HGG patients are still alive with median follow-up(FU) of 35.7 months (range 12.1-85.6) Median overall survival (OS) was 13.5 months (range 1.4-85.6) All patients with MB/PNET died (median OS 5.7 months, range 4.3-51.2) One patient with ependymoma is still alive at 22.3 months FU The other three patients died at, respectively, 7.7, 30.1 and 31.5 months Two patients with ATRT are still alive at, respectively, 34.1 and 52.6 months FU The third patient died at 50.5 months NO severe adverse events were noticed Conclusions. In this exploratory study, HGG and ATRT seem to respond favourably to vaccination than MB/PNET and ependymoma Although preliminary, our results are promising and support further testing of DC-based immunotherapy in new treatment protocols for HGG and ATRT Pediatr Blood Cancel 2010,54 519-525 (C) 2009 Wiley-Liss, Inc
引用
收藏
页码:519 / 525
页数:7
相关论文
共 43 条
[1]   Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].
Bao, Shideng ;
Wu, Qiulian ;
McLendon, Roger E. ;
Hao, Yueling ;
Shi, Qing ;
Hjelmeland, Anita B. ;
Dewhirst, Mark W. ;
Bigner, Darell D. ;
Rich, Jeremy N. .
NATURE, 2006, 444 (7120) :756-760
[2]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[3]   Atypical teratoid/rhabdoid tumor of the central nervous system: A highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma - A pediatric oncology group study [J].
Burger, PC ;
Yu, IT ;
Tihan, T ;
Friedman, HS ;
Strother, DR ;
Kepner, JL ;
Duffner, PK ;
Kun, LE ;
Perlman, EJ .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1998, 22 (09) :1083-1092
[4]   Recurrent supratentorial malignant gliomas in children - Long-term salvage therapy with oral etoposide [J].
Chamberlain, MC .
ARCHIVES OF NEUROLOGY, 1997, 54 (05) :554-558
[5]   Immunotherapy for malignant gliomas: emphasis on strategies of active specific immunotherapy using autologous dendritic cells [J].
De Vleeschouwer, S ;
Van Gool, SW ;
Van Calenbergh, F .
CHILDS NERVOUS SYSTEM, 2005, 21 (01) :7-18
[6]   Uptake and presentation of malignant glioma tumor cell lysates by monocyte-derived dendritic cells [J].
De Vleeschouwer, S ;
Arredouani, M ;
Adé, M ;
Cadot, P ;
Vermassen, E ;
Ceuppens, JL ;
Van Gool, SW .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2005, 54 (04) :372-382
[7]   Transient local response and persistent tumor control in a child with recurrent malignant glioma: treatment with combination therapy including dendritic cell therapy - Case report [J].
De Vleeschouwer, S ;
Van Calenbergh, F ;
Demaerel, P ;
Flamen, P ;
Rutkowski, S ;
Kaempgen, E ;
Wolff, JE ;
Plets, C ;
Sciot, R ;
Van Gool, SW .
JOURNAL OF NEUROSURGERY, 2004, 100 (05) :492-497
[8]   Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme [J].
De Vleeschouwer, Steven ;
Fieuws, Steffen ;
Rutkowski, Stefan ;
Van Calenbergh, Frank ;
Van Loon, Johannes ;
Goffin, Jan ;
Sciot, Raf ;
Wilms, Guido ;
Demaerel, Philippe ;
Warmuth-Metz, Monika ;
Soerensen, Niels ;
Wolff, Johannes E. A. ;
Wagner, Sabine ;
Kaempgen, Eckhart ;
Van Gool, Stefaan W. .
CLINICAL CANCER RESEARCH, 2008, 14 (10) :3098-3104
[9]   Dendritic cell vaccination in patients with malignant gliomas: Current status and future directions [J].
de Vleeschouwer, Steven ;
Rapp, Marion ;
Sorg, Ruediger V. ;
Steiger, Hans-Jakob ;
Stummer, Walter ;
van Gool, Stefaan .
NEUROSURGERY, 2006, 59 (05) :988-999
[10]   Chemotherapy resistance of glioblastoma stem cells [J].
Eramo, A. ;
Ricci-Vitiani, L. ;
Zeuner, A. ;
Pallini, R. ;
Lotti, F. ;
Sette, G. ;
Pilozzi, E. ;
Larocca, L. M. ;
Peschle, C. ;
De Maria, R. .
CELL DEATH AND DIFFERENTIATION, 2006, 13 (07) :1238-1241