NDLI: ROBUST INDUCTION OF TYPE-1 CD8+ T-CELL RESPONSES IN WHO GRADE II LOW-GRADE GLIOMA PATIENTS RECEIVING PEPTIDE-BASED VACCINES IN COMBINATION WITH POLY-ICLC

Content Provider	PubMed Central
Author	Okada, Hideho Butterfield, Lisa H. Hamilton, Ronald L. Aki, Hoji Sakaki, Masashi Ahn, Brian J. Gary, Kohanbash Jan, Drappatz Engh, Johnathan Nduka, Amankulor Lively, Mark O. Chan, Michael D. Salazar, Andres M. Potter, Douglas M. Shaw, Edward G. Lieberman, Frank S.
Copyright Year	2014
Abstract	BACKGROUND: WHO grade II low-grade gliomas (LGGs) with high risk factors for recurrence are mostly lethal despite current treatments, and novel approaches are needed. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in human leukocyte antigen (HLA)-A2+ adults with high-risk LGGs in the following three cohorts: 1) newly diagnosed patients without prior radiation therapy (RT); 2) newly diagnosed patients with prior RT, and 3) recurrent patients. METHODS: GAAs were interleukin-13 receptor (IL-13R)α2, EphA2, Wilms Tumor (WT)1, and Survivin, and synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for 8 courses with intramuscular injections of Toll-like receptor 3 agonist Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose (poly-ICLC), followed by q12-week booster vaccines. Primary endpoints were safety and CD8+ T-cell responses against vaccine-targeted GAAs. RESULTS: Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity has been encountered except for one case with Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 fever (Cohort 1). Enzyme-linked Immuno-SPOT (ELISPOT) assays demonstrated robust and sustained interferon (IFN)-γ responses against at least 3 of the 4 GAA epitopes in 10 and 4 cases of Cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFN-γ ELISPOT responses than Cohort 3 patients, suggesting newly diagnosed patients have superior vaccine-responsiveness to recurrent patients. IFN-γ ELISPOT response levels in this study is significantly higher than those observed in our previous phase I/II study in high-grade glioma patients (Okada et al. JCO 2011). Furthermore, IFN-γ ELISPOT response levels were significantly higher than those for IL-5, indicating effective type-1 skewing by the current regimen. Median progression-free survival (PFS) periods are 21 months (Cohort 1; since diagnosis; range 10-42) and 12 months (Cohort 3; since the 1st vaccine; range 3-26). The only patient with large astrocytoma in Cohort 2 has been progression-free for over 58 months since diagnosis. There was a positive trend between IFN-γ ELISPOT responses and progression-free survival (PFS) in Cohort 3 patients (P = 0.08 by The Cox proportional hazards model). CONCLUSIONS: The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade II LGG patients. These results suggest these patients may be suitable populations for vaccine therapy and warrant further evaluations of this approach. SECONDARY CATEGORY: Clinical Neuro-Oncology.
Related Links	http://dx.doi.org/10.1093/neuonc/nou208.62
Starting Page	39
File Format	PDF
ISSN	15228517
e-ISSN	15235866
Journal	Neuro-Oncology
Issue Number	Suppl 3
Volume Number	16
Language	English
Publisher	Oxford University Press
Publisher Date	2014-07-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Cancer Research Oncology Clinical Neurology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Neurology (clinical) Oncology

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