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Glioma-Associated Antigen Peptide Vaccination Produces Antigen-Specific T-Cell Response and Clinical Activity in Children With High-Grade Gliomas

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Key Points

  • GAA peptide vaccination was associated with immunologic response and evidence of clinical activity.
  • Symptomatic pseudoprogression was observed in some patients and was associated with prolonged survival. 

In a study reported in the Journal of Clinical Oncology, Pollack et al found antigen-specific immune responses and evidence of clinical activity with glioma-associated antigen (GAA) peptide vaccination in children with newly diagnosed malignant brainstem and nonbrainstem gliomas.

Study Details

In this pilot study, HLA-A2–positive children with newly diagnosed brainstem gliomas or other high-grade gliomas received SC vaccination with GAA epitope peptides using GAAs identified by the investigators as commonly overexpressed in pediatric gliomas. The GAAs consisted of EphA2, interleukin-13 receptor α 2 (IL-13Rα2), and survivin.

The peptide epitopes were emulsified in Montanide-ISA-51 and administered with intramuscular polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose every 3 weeks for eight courses, followed by booster vaccinations every 6 weeks. T-cell responses against vaccine-targeted GAA epitopes were measured, and treatment response was assessed by clinical evaluation and magnetic resonance imaging.

Safety

A total of 26 children were enrolled, including 14 with brainstem gliomas and 12 with other high-grade gliomas treated with irradiation and concurrent chemotherapy. Vaccination was generally well tolerated, and no dose-limiting non–central nervous system toxicities were observed.

The main toxicities were grade 1 and 2 injection-site reactions (100%) and flu-like symptoms (fatigue, myalgia, fever, chills, and headache, in 92%), which were usually limited to 24 to 48 hours after each vaccination, and grade 1 gastrointestinal symptoms (31%).

Responses

Five patients had symptomatic pseudoprogression, which responded to dexamethasone and was associated with prolonged survival. One patient had a subsequent partial response and survived for 19.5 months, and the remainder had survival durations of 11.3, 18.4, 19.5, and > 38.0 months. Two patients had progressive disease during the first two vaccine courses. Nineteen had stable disease, two had partial response, one had minor response, and two had prolonged disease-free periods following surgery.

Analysis in 21 patients showed anti-GAA T-cell responses in 13, including response to IL-13Rα2 in 10, EphA2 in 11, and survivin in 3.

The investigators concluded, “GAA peptide vaccination in children with gliomas is generally well tolerated and has preliminary evidence of immunologic and clinical responses. Careful monitoring and management of pseudoprogression is essential.”

The study was supported by grants from the National Institutes of Health and University of Pittsburgh Cancer Institute Immunologic Monitoring and Cellular Products Laboratory and by the Pediatric Low-Grade Glioma Initiative via the National Brain Tumor Society and the Ellie Kavalieros Fund of the Children’s Hospital of Pittsburgh Foundation.

Ian F. Pollack, MD, of Children’s Hospital of Pittsburgh, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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