Journal of Neuro-Oncology

, Volume 130, Issue 3, pp 517–527 | Cite as

Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study

  • Ian F. Pollack
  • Regina I. Jakacki
  • Lisa H. Butterfield
  • Ronald L. Hamilton
  • Ashok Panigrahy
  • Daniel P. Normolle
  • Angela K. Connelly
  • Sharon Dibridge
  • Gary Mason
  • Theresa L. Whiteside
  • Hideho Okada
Clinical Study


Recurrent high-grade gliomas (HGGs) of childhood have an exceedingly poor prognosis with current therapies. Accordingly, new treatment approaches are needed. We initiated a pilot trial of vaccinations with peptide epitopes derived from glioma-associated antigens (GAAs) overexpressed in these tumors in HLA-A2+ children with recurrent HGG that had progressed after prior treatments. Peptide epitopes for three GAAs (EphA2, IL13Rα2, survivin), emulsified in Montanide-ISA-51, were administered subcutaneously adjacent to intramuscular injections of poly-ICLC every 3 weeks for 8 courses, followed by booster vaccines every 6 weeks. Primary endpoints were safety and T-cell responses against the GAA epitopes, assessed by enzyme-linked immunosorbent spot (ELISPOT) analysis. Treatment response was evaluated clinically and by magnetic resonance imaging. Twelve children were enrolled, 6 with glioblastoma, 5 with anaplastic astrocytoma, and one with malignant gliomatosis cerebri. No dose-limiting non-CNS toxicity was encountered. ELISPOT analysis, in ten children, showed GAA responses in 9: to IL13Rα2 in 4, EphA2 in 9, and survivin in 3. One child had presumed symptomatic pseudoprogression, discontinued vaccine therapy, and responded to subsequent treatment. One other child had a partial response that persisted throughout 2 years of vaccine therapy, and continues at >39 months. Median progression-free survival (PFS) from the start of vaccination was 4.1 months and median overall survival (OS) was 12.9 months. 6-month PFS and OS were 33 and 73 %, respectively. GAA peptide vaccination in children with recurrent malignant gliomas is generally well tolerated, and has preliminary evidence of immunological and modest clinical activity.


Astrocytoma Glioma Immunotherapy Pediatric brain tumor Vaccine therapy 



UPCI Clinical Research Services for regulatory management, Andres Salazar, Oncovir, Inc., for provision of poly-ICLC, physicians who referred their patients, and the patients and families who participated in this trial.


This study was supported by National Institutes of Health grants R21CA149872, P01NS40923, and the UPCI Immunologic Monitoring and Cellular Products Laboratory, supported in part by NIH award P30CA47904, and the Pediatric Clinical and Translational Research Center, supported by the NIH through Grant Numbers UL1 RR024153 and UL1TR000005. Support was also provided by grants from the Pediatric Low-Grade Glioma Initiative via the National Brain Tumor Society, the Ellie Kavalieros Fund, the Connor’s Cure Fund, the Ian Yagoda’s Friends Foundation, and the Translational Brain Tumor Fund of the Children’s Hospital of Pittsburgh Foundation.

Compliance with ethical standards

Conflict of interest

Hideho Okada is an inventor in the U.S. Patent Application No. 60,611,797 (Utility Patent Application) “Identification of An IL-13 Receptor Alpha2 Peptide Analogue Capable of Enhancing Stimulation of Glioma-Specific CTL Response”. An exclusive licensing agreement has been completed on this application between University of Pittsburgh and Stemline, Inc. Due to the potential conflicts of interest, Hideho Okada did not solely interpret any data in the current study. Dr. Regina I. Jakacki is currently employed by Astra Zeneca.

Informed consent

Signed IRB-approved informed consent was required both for HLA-A2 screening and initiation of therapy.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ian F. Pollack
    • 1
    • 8
    • 9
  • Regina I. Jakacki
    • 2
    • 9
  • Lisa H. Butterfield
    • 4
    • 5
    • 7
    • 9
  • Ronald L. Hamilton
    • 3
    • 9
  • Ashok Panigrahy
    • 6
    • 9
  • Daniel P. Normolle
    • 10
  • Angela K. Connelly
    • 2
  • Sharon Dibridge
    • 2
  • Gary Mason
    • 2
    • 9
  • Theresa L. Whiteside
    • 3
    • 7
    • 9
  • Hideho Okada
    • 1
    • 5
    • 7
    • 9
    • 11
  1. 1.Department of NeurosurgeryUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of PediatricsUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Department of PathologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  5. 5.Department of SurgeryUniversity of Pittsburgh School of MedicinePittsburghUSA
  6. 6.Department of RadiologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  7. 7.Department of ImmunologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  8. 8.Department of Neurosurgery, Children’s Hospital of PittsburghUniversity of PittsburghPittsburghUSA
  9. 9.University of Pittsburgh Cancer InstituteUniversity of Pittsburgh School of MedicinePittsburghUSA
  10. 10.Department of BiostatisticsGraduate School of Public Health, University of PittsburghPittsburghUSA
  11. 11.Department of NeurosurgeryUniversity of CaliforniaSan FranciscoUSA

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