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

摘要: Purpose: WHO grade 2 low-grade gliomas (LGG) 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 synthetic peptides glioma-associated antigen (GAA) epitopes in HLA-A2 + adults high-risk LGGs following three cohorts: (i) patients without prior progression, chemotherapy, or radiotherapy (RT); (ii) progression chemotherapy but RT; (iii) recurrent patients. Experimental Design: GAAs were IL13Rα2, EphA2, WT1, Survivin. Synthetic emulsified Montanide-ISA-51 given every 3 weeks eight courses intramuscular injections poly-ICLC, followed by q12 week booster vaccines. Results: Cohorts 1, 2, enrolled 12, 10 patients, respectively. No regimen-limiting toxicity was encountered except one case fever, fatigue, mood disturbance (cohort 1). ELISPOT assays demonstrated robust IFNγ responses against at least four GAA 4 cases cohorts 1 3, Cohort significantly higher than cohort Median progression-free survival (PFS) periods since first vaccine 17 months (range, 10–47+) 12 3–41+). The only patient large astrocytoma has been more 67 diagnosis. Conclusion: regimen is well tolerated induces GAA-specific glioma These results warrant further evaluations this approach. Clin Cancer Res; 21(2); 286–94. ©2014 AACR .