Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy

被引:67
|
作者
Zhang, Jian Gang [1 ,2 ]
Kruse, Carol A. [3 ]
Driggers, Lara [1 ]
Hoa, Neil [1 ,2 ]
Wisoff, Jeffrey [4 ,5 ]
Allen, Jeffrey C. [5 ,6 ,7 ]
Zagzag, David [4 ,7 ,8 ,9 ]
Newcomb, Elizabeth W. [7 ,9 ]
Jadus, Martin R. [1 ,2 ,10 ]
机构
[1] Vet Affairs Med Ctr, Lab Serv, Long Beach, CA USA
[2] Univ Calif Irvine, Dept Pathol, Irvine, CA 92717 USA
[3] Sidney Kimmel Canc Ctr, San Diego, CA USA
[4] NYU, Sch Med, Dept Neurosurg, New York, NY USA
[5] NYU, Sch Med, Dept Pediat, New York, NY USA
[6] NYU, Sch Med, Dept Neurol, New York, NY USA
[7] NYU, Ctr Canc, New York, NY USA
[8] NYU, Sch Med, Dept Neuropathol, New York, NY USA
[9] NYU, Sch Med, Dept Pathol, New York, NY USA
[10] Chao Comprehens Canc Ctr, Div NeuroOncol, Orange, CA USA
关键词
glioma; pediatric brain tumors; tumor associated antigens; immunotherapy;
D O I
10.1007/s11060-008-9534-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives We evaluated and compared tumor antigen precursor protein (TAPP) profiles in adult and pediatric brain tumors of 31 genes related to tumor associated antigens (TAA) for possible use in immunotherapy. Antigens were selected based on their potential to stimulate T cell responses against tumors of neuroectodermal origin. Methods Thirty-seven brain tumor specimens from 11 adult and 26 pediatric patients were analyzed by quantitative real-time PCR for the relative expression of 31 TAPP mRNAs. The age range of adults (4F:7M) was 27-77 years (median 51.5 +/- 14.5 years) and for pediatrics (12F:14M) was 0.9-19 years (median 8.3 +/- 5.5 years). Histological diagnoses consisted of 16 glioblastomas, 4 low grade astrocytomas, 10 juvenile pilocytic astrocytomas, and 7 ependymomas. Results The adult gliomas expressed 94% (29 of 31) of the TAPP mRNAs evaluated compared with pediatric brain tumors that expressed 55-74% of the TAPP mRNAs, dependent on tumor histological subtype. Four types of TAPP expression patterns were observed: (1) equal expression among adult and pediatric cases, (2) greater expression in adult than pediatric cases, (3) expression restricted to adult GBM and (4) a random distribution. The pediatric brain tumors lacked expression of some genes associated with engendering tumor survival, such as hTert and Survivin. Conclusions The potential TAA targets identified from the TAPP profiles of 31 genes associated with adult and pediatric brain tumors may help investigators select specific target antigens for developing dendritic cell- or peptide-based vaccines or T cell-based immunotherapeutic approaches against brain tumors.
引用
收藏
页码:65 / 76
页数:12
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