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

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Abstract

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.

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Acknowledgements

This work was partially supported by a Veterans Affairs Merit Review grant [MRJ], the Long Island League to Abolish Cancer Fund [EWN] and National Institutes of Health grants NS057829 [EWN], NS046463, CA121258, NS054093, NS056300, and The R. Herbert & Alma S. Manweiler Memorial Research Fund [CAK] and the Making Headway Foundation [DZ].

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Authors and Affiliations

  1. Department of Pathology, University of California at Irvine, Irvine, CA, USA

    Jian Gang Zhang, Neil Hoa & Martin R. Jadus

  2. Lab Service, Veterans Affairs Medical Center, Long Beach, CA, USA

    Jian Gang Zhang, Lara Driggers, Neil Hoa & Martin R. Jadus

  3. Sidney Kimmel Cancer Center, San Diego, CA, USA

    Carol A. Kruse

  4. Departments of Neurosurgery and Pediatrics, New York University School of Medicine, New York, NY, USA

    Jeffrey Wisoff

  5. Departments of Pediatrics and Neurology, New York University School of Medicine, New York, NY, USA

    Jeffrey C. Allen

  6. New York University Cancer Center, New York, NY, USA

    Jeffrey C. Allen, David Zagzag & Elizabeth W. Newcomb

  7. Departments of Neurosurgery and Neuropathology, New York University School of Medicine, New York, NY, USA

    David Zagzag

  8. Department of Pathology, New York University School of Medicine, New York, NY, USA

    David Zagzag & Elizabeth W. Newcomb

  9. Division of NeuroOncology, Chao Comprehensive Cancer Center, Orange, CA, USA

    Martin R. Jadus

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  1. Jian Gang Zhang
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Correspondence to Martin R. Jadus.

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Elizabeth W. Newcomb and Martin R. Jadus contributed equally as senior authors.

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Zhang, J.G., Kruse, C.A., Driggers, L. et al. Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy. J Neurooncol 88, 65–76 (2008). https://doi.org/10.1007/s11060-008-9534-4

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  • DOI: https://doi.org/10.1007/s11060-008-9534-4

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