title: Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapy.
abstract: Despite surgery and radiotherapy, as many as 50 % of children with ependymomas will suffer from tumor recurrences that will ultimately lead to death. Our group's initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing. We therefore investigated whether EphA2, IL-13Rα2, Survivin, and, additionally, Wilms' Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable. Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas. Normal brain and ependyma were used for background staining controls. Negative staining was defined as no staining or staining equaling the background intensity in normal brain tissues. In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1. Only 3 of 19 cases were positive for two or fewer tumor-associated antigens (TAAs); 16 of 19 cases were positive for three or more TAAs. In the 13 adult cases, all 13 demonstrated positive staining for EphA2, IL-13Rα2, and Survivin. Only 2 of 13 cases (15 %) demonstrated positive staining for WT1. All adult specimens were positive for three or more TAAs. Some ependymomas showed patchy variability in intensity. Pediatric and adult ependymomas frequently express EphA2, IL-13Rα2, and Survivin. This provides the basis for the utilization of an established multiple peptide vaccine for ependymoma in a clinical trial setting.
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Jacky T
authors.initials: JT
authors.lastname: Yeung
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
authors.forename: Hideho
authors.initials: H
authors.lastname: Okada
authors.forename: Regina I
authors.initials: RI
authors.lastname: Jakacki
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000473:pathology*; D019496:Cancer Vaccines; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D036104:Receptor, EphA2 / Q000378:metabolism; D000077022:Survivin; D025721:WT1 Proteins / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; C508181:IL13RA1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D053661:Interleukin-13 Receptor alpha1 Subunit; D000077022:Survivin; D025721:WT1 Proteins; D036104:Receptor, EphA2