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  • Results of A Pilot Study of Vaccinations with HLA-A2-Restricted Glioma Antigen-Peptides in Combination with Poly-ICLC for Children with Newly Diagnosed Malignant Brain Stem Gliomas, Non-Brainstem High

    Final Number:
    196

    Authors:
    Ian F. Pollack MD; Regina Jakacki; Lisa H. Butterfield; Hideho Okada MD, PhD

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: Malignant astrocytomas are among the most common and deadly brain tumors of childhood, and most children succumb within several years of diagnosis, despite current treatments. New therapeutic approaches are needed that target the unique features of these tumors. During the last decade, we have gained significant preclinical and clinical experience with immunotherapy for adult gliomas, and extended these insights to the treatment of childhood gliomas, based on our observation of substantial similarities between these tumors in their expression of selected glioma-associated antigens (GAAs).

    Methods: Building upon these data, we initiated a pilot trial of subcutaneous vaccinations with synthetic peptides for GAA epitopes emulsified in Montanide-ISA-51 every 3 weeks for 8 courses, and intramuscular administration of poly-ICLC on the day of each vaccination in HLA-A2+ children with newly diagnosed malignant brainstem gliomas, non-brainstem malignant gliomas, or recurrent gliomas. GAAs for these peptides were EphA2, interleukin (IL)-13 receptor-a2, and survivin. The primary endpoints were safety and T cell responses against the vaccine-targeted GAAs. Preliminary data on treatment response was evaluated clinically and by MR imaging.

    Results: To date, 14 patients have been treated on this protocol. Toxicities have been principally limited to fatigue, injection site reactions, and low-grade fever. ELISPOT assays have been completed in three patients and have demonstrated positive responses to IL13Ra2 and EphA2 in two patients. Additional ELISPOT and tetramer assays will be performed as the patients complete vaccination or come off study. Eleven of 14 patients have exceeded the expected median progression-free survival for brainstem or high-grade gliomas, and five remain on long-term maintenance vaccine therapy with either stable disease (4) or objective tumor regression (1).

    Conclusions: Our preliminary results demonstrate that a multipeptide approach to vaccination in children with gliomas is well tolerated, and has evidence of both immunological and clinical activity.

    Patient Care: This trial will form the basis for a phase II study designed to further assess clinical and immunological efficacy of this innovative approach.

    Learning Objectives: Participants should be able: 1) Understand the rationale for vaccine-based immunotherapy as a treatment strategy for gliomas; 2) Gain familiarity with the issues underlying immunological response and corrrelative laboratory monitoring; 3) Be familiar with the results of the current trial.

    References:

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