Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC.
Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC.
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DOI：
10.1158/1078-0432.ccr-14-1790
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发表时间：
2015-01-15
期刊：
影响因子：
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通讯作者：
Lieberman FS
中科院分区：
文献类型：
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作者：
Okada H;Butterfield LH;Hamilton RL;Hoji A;Sakaki M;Ahn BJ;Kohanbash G;Drappatz J;Engh J;Amankulor N;Lively MO;Chan MD;Salazar AM;Shaw EG;Potter DM;Lieberman FS
WHO grade II low-grade gliomas (LGGs) with high risk factors for recurrence are mostly lethal despite current treatments. 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 HLA-A2+ adults with high-risk LGGs in the following three cohorts: 1) patients without prior progression, chemotherapy or radiation therapy (RT); 2) patients without prior progression or chemotherapy but with prior RT, and 3) recurrent patients. GAAs were IL-13Rα2, EphA2, WT1, and Survivin. Synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for 8 courses with intramuscular injections of poly-ICLC, followed by q12week booster vaccines. Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity was encountered except for one case with Grade 3 fever, fatigue and mood disturbance (Cohort 1). ELISPOT assays demonstrated robust 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 responses than Cohort 3 patients. Median progression-free survival (PFS) periods since the 1st vaccine are 17 months in Cohort 1 (range 10–47+) and 12 months in Cohort 3 (range 3–41+). The only patient with large astrocytoma in Cohort 2 has been progression-free for over 67 months since diagnosis. The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade II glioma patients. These results warrant further evaluations of this approach.
