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Abstract Details

AbstractDetails

Abstract Date: 5/1/2016

Author(s):
Ian F. Pollack, MD
Regina Jakacki, MD
Lisa Butterfield, PhD
Ronald Hamilton, MD
Ashok Panigrahy, MD
Daniel Normolle, PhD
Angela Connelly, BS
Sharon DiBridge, BS
Gary Mason, MD
Theresa Whiteside, PhD
Hideho Okada, MD, PhD (Pittsburgh, PA)

Introduction

Low-grade gliomas (LGG) are the most common childhood brain tumors. Although resection is curative for well-circumscribed superficial lesions, tumors that are infiltrative or arise from deep structures are challenging, and prone to recurrences leading to cumulative morbidity. Accordingly, new treatment approaches are needed. Having identified a panel of glioma-associated antigens (GAAs) overexpressed in these tumors, we initiated a novel pilot trial of vaccinations with peptides for GAA epitopes in HLA-A2+ children with recurrent LGG that had progressed after >2 prior regimens.


Methods

Peptide epitopes for three GAAs (EphA2, IL13Rα2, survivin) were emulsified in Montanide-ISA-51 and 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-lymphocyte responses against GAA epitopes. Treatment response was evaluated clinically and by magnetic resonance imaging.


Results

Fourteen children were enrolled. Other than grade 3 urticaria in one child, no regimen-limiting toxicity was encountered. Vaccination induced immunoreactivity to at least one vaccine-targeted antigen in all 11 evaluable patients: to IL13Rα2 in 3, EphA2 in 10, and survivin in 3. One child with a metastatic LGG had asymptomatic pseudoprogression 6 weeks after starting vaccination, and subsequently had dramatic disease regression with >75% shrinkage of the primary tumor and regression of all metastatic disease, persisting >52 months. Three other children had sustained partial responses, ongoing at 41 and 27 and 6 months, and one had a transient response. A trend was noted between ELISPOT response and progression-free survival. Patients with positive ELISPOT responses to two or more antigens were more likely to have objective responses than those responding to a single antigen (p = 0.03, Fisher’s exact test).

Conclusion:

GAA peptide vaccination in children with recurrent LGGs is well tolerated, with preliminary evidence of immunological and clinical activity.

Keywords:

Article ID: AA-34746


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