Immune responses and outcome after vaccination with glioma-associated antigen peptides and poly-ICLC in a pilot study for pediatric recurrent low-grade gliomas†. Issue 8 (15th March 2016)

• Record Type: Journal Article
• Authors: Pollack, Ian F.; Jakacki, Regina I.; Butterfield, Lisa H.; Hamilton, Ronald L.; Panigrahy, Ashok; Normolle, Daniel P.; Connelly, Angela K.; Dibridge, Sharon; Mason, Gary; Whiteside, Theresa L.; Okada, Hideho
• Is Part Of: Neuro-oncology. Volume 18:Issue 8(2016:Aug.)
• Page Start: 1157
• Page End: 1168
• Publication Date: 2016-03-15
• Subjects: astrocytoma -- glioma -- immunotherapy -- pediatric brain tumor -- vaccine therapy; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/now026
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Low-grade gliomas (LGGs) are the most common brain tumors of childhood. Although surgical resection is curative for well-circumscribed superficial lesions, tumors that are infiltrative or arise from deep structures are therapeutically challenging, and new treatment approaches are needed. Having identified a panel of glioma-associated antigens (GAAs) overexpressed in these tumors, we initiated a pilot trial of vaccinations with peptides for GAA epitopes in human leukocyte antigen–A2+ children with recurrent LGG that had progressed after at least 2 prior regimens. Methods: Peptide epitopes for 3 GAAs (EphA2, IL-13Rα2, and survivin) were emulsified in Montanide-ISA-51 and administered subcutaneously adjacent to intramuscular injections of polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose 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 MRI. 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 GAA in all 12 evaluable patients: to IL-13Rα2 in 3, EphA2 in 11, and survivin in 3. One child with a metastatic LGG had asymptomatic pseudoprogression noted 6 weeks after starting vaccination, followed by dramatic disease regression with >75% shrinkage of primary tumor and regression of metastatic disease, persisting >57 months. Three other children had sustained partial responses, lasting >10, >31, and >45 months, and one had a transient response. Conclusions: GAA peptide vaccination in children with recurrent LGGs is generally well tolerated, with preliminary evidence of immunological and clinical activity.