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Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy

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Abstract

Despite surgery and radiotherapy, as many as 50 % of children with ependymomas will suffer from tumor recurrences that will ultimately lead to death. Our group’s initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing. We therefore investigated whether EphA2, IL-13Rα2, Survivin, and, additionally, Wilms’ Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable. Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas. Normal brain and ependyma were used for background staining controls. Negative staining was defined as no staining or staining equaling the background intensity in normal brain tissues. In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1. Only 3 of 19 cases were positive for two or fewer tumor-associated antigens (TAAs); 16 of 19 cases were positive for three or more TAAs. In the 13 adult cases, all 13 demonstrated positive staining for EphA2, IL-13Rα2, and Survivin. Only 2 of 13 cases (15 %) demonstrated positive staining for WT1. All adult specimens were positive for three or more TAAs. Some ependymomas showed patchy variability in intensity. Pediatric and adult ependymomas frequently express EphA2, IL-13Rα2, and Survivin. This provides the basis for the utilization of an established multiple peptide vaccine for ependymoma in a clinical trial setting.

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Acknowledgments

We thank Maki Ikeura, BS for providing support with immunohistochemistry. This work was supported by a grant from the Doris Duke Charitable Foundation to University of Pittsburgh to J.Y. and a grant from National Institute of Health (R21 CA149872-02) to R.H. and I.P.

Ethical standards

This study complies with the current laws of the country in which they were performed.

Conflict of interest

The authors do not have any conflict of interest to declare.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jacky T. Yeung, Hideho Okada & Ian F. Pollack

  2. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Ronald L. Hamilton

  3. Departments of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Regina I. Jakacki

  4. Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA

    Ian F. Pollack

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  1. Jacky T. Yeung
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  2. Ronald L. Hamilton
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  4. Regina I. Jakacki
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  5. Ian F. Pollack
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Correspondence to Ian F. Pollack.

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Yeung, J.T., Hamilton, R.L., Okada, H. et al. Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy. J Neurooncol 111, 103–111 (2013). https://doi.org/10.1007/s11060-012-0998-x

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  • DOI: https://doi.org/10.1007/s11060-012-0998-x

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