期刊
JOURNAL OF CLINICAL ONCOLOGY
卷 32, 期 19, 页码 2050-U99出版社
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2013.54.0526
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资金
- National Institutes of Health (NIH) [R21CA149872, P01NS40923]
- University of Pittsburgh Cancer Institute Immunologic Monitoring and Cellular Products Laboratory from NIH [P30CA47904]
- Pediatric Low-Grade Glioma Initiative via the National Brain Tumor Society
- Ellie Kavalieros Fund of the Children's Hospital of Pittsburgh Foundation
- Pediatric Clinical and Translational Research Center from NIH [UL1 RR024153, UL1TR000005]
Purpose Diffuse brainstem gliomas (BSGs) and other high-grade gliomas (HGGs) of childhood carry a dismal prognosis despite current treatments, and new therapies are needed. Having identified a series of glioma-associated antigens (GAAs) commonly overexpressed in pediatric gliomas, we initiated a pilot study of subcutaneous vaccinations with GAA epitope peptides in HLA-A2-positive children with newly diagnosed BSG and HGG. Patients and Methods GAAs were EphA2, interleukin-13 receptor alpha 2 (IL-13R alpha 2), and survivin, and their peptide epitopes were emulsified in Montanide-ISA-51 and given every 3 weeks with intramuscular polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose for eight courses, followed by booster vaccinations every 6 weeks. Primary end points were safety and T-cell responses against vaccine-targeted GAA epitopes. Treatment response was evaluated clinically and by magnetic resonance imaging. Results Twenty-six children were enrolled, 14 with newly diagnosed BSG treated with irradiation and 12 with newly diagnosed BSG or HGG treated with irradiation and concurrent chemotherapy. No dose-limiting non-CNS toxicity was encountered. Five children had symptomatic pseudoprogression, which responded to dexamethasone and was associated with prolonged survival. Only two patients had progressive disease during the first two vaccine courses; 19 had stable disease, two had partial responses, one had a minor response, and two had prolonged disease-free status after surgery. Enzyme-linked immunosorbent spot analysis in 21 children showed positive anti-GAA immune responses in 13: to IL-13R alpha 2 in 10, EphA2 in 11, and survivin in three. Conclusion 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. (C) 2014 by American Society of Clinical Oncology
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