Malignant astrocytomas are among the most common and deadly brain tumors of childhood. Most children with brainstem and subtotally resected non-brainstem malignant gliomas die within several years of diagnosis, despite current treatments. Accordingly, new treatment approaches are needed that target the unique features of these tumors. During the last decade, we have gained significant preclinical and clinical experience with immunotherapy for adult gliomas, and propose to extend these insights to the treatment of childhood malignant gliomas, based on our observation of substantial similarities between these tumors in their expression of glioma-associated antigens (GAAs). Building upon these data, we propose the use of a GAA- based vaccine cocktail, combined with an immunoadjuvant (poly-ICLC), for children with newly diagnosed malignant brainstem gliomas (Stratum 1) and subtotally resected non-brainstem malignant gliomas (Stratum 2). Participants will be treated with s.c. injections of GAA vaccines every 3 weeks for 8 courses and poly-ICLC will be administered (30

Public Health Relevance

Our clinical study and biological correlative analyses will represent the first application of a multipeptide epitope vaccine-based strategy to a pediatric glioma cohort, providing fundamental data for assessing safety, and clinical and immunological efficacy, of immunotherapeutic strategies in the pediatric brain tumor context.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA149872-02
Application #
8020082
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Timmer, William C
Project Start
2010-03-01
Project End
2013-02-28
Budget Start
2011-03-03
Budget End
2013-02-28
Support Year
2
Fiscal Year
2011
Total Cost
$304,932
Indirect Cost
Name
University of Pittsburgh
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Furtado, Andre D; Ceschin, Rafael; Bl├╝ml, Stefan et al. (2017) Neuroimaging of Peptide-based Vaccine Therapy in Pediatric Brain Tumors: Initial Experience. Neuroimaging Clin N Am 27:155-166
Pollack, Ian F; Jakacki, Regina I; Butterfield, Lisa H et al. (2016) Immune responses and outcome after vaccination with glioma-associated antigen peptides and poly-ICLC in a pilot study for pediatric recurrent low-grade gliomas. Neuro Oncol 18:1157-68
Pollack, Ian F; Jakacki, Regina I; Butterfield, Lisa H et al. (2016) Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study. J Neurooncol 130:517-527
Ceschin, R; Kurland, B F; Abberbock, S R et al. (2015) Parametric Response Mapping of Apparent Diffusion Coefficient as an Imaging Biomarker to Distinguish Pseudoprogression from True Tumor Progression in Peptide-Based Vaccine Therapy for Pediatric Diffuse Intrinsic Pontine Glioma. AJNR Am J Neuroradiol 36:2170-6
Pollack, Ian F; Jakacki, Regina I; Butterfield, Lisa H et al. (2014) Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and n J Clin Oncol 32:2050-8
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Okada, Hideho; Pollack, Ian F (2011) Do we need novel radiologic response criteria for brain tumor immunotherapy? Expert Rev Neurother 11:619-22