Details

Autor(en) / Beteiligte

• Batich, Kristen A
• Reap, Elizabeth A
• Archer, Gary E
• Sanchez-Perez, Luis
• Nair, Smita K
• Schmittling, Robert J
• Norberg, Pam
• Xie, Weihua
• Herndon, 2nd, James E
• Healy, Patrick
• McLendon, Roger E
• Friedman, Allan H
• Friedman, Henry S
• Bigner, Darell
• Vlahovic, Gordana
• Mitchell, Duane A
• Sampson, John H

Titel

Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination

Ist Teil von

• Clinical cancer research, 2017-04, Vol.23 (8), p.1898-1909

Ort / Verlag

United States: American Association for Cancer Research Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS). Following standard-of-care, 11 patients with newly diagnosed glioblastoma received DI-TMZ (100 mg/m /d × 21 days per cycle) with at least three vaccines of pp65 lysosome-associated membrane glycoprotein mRNA-pulsed DCs admixed with GM-CSF on day 23 ± 1 of each cycle. Thereafter, monthly DI-TMZ cycles and pp65-DCs were continued if patients had not progressed. Following DI-TMZ cycle 1 and three doses of pp65-DCs, pp65 cellular responses significantly increased. After DI-TMZ, both the proportion and proliferation of regulatory T cells (Tregs) increased and remained elevated with serial DI-TMZ cycles. Median PFS and OS were 25.3 months [95% confidence interval (CI), 11.0-∞] and 41.1 months (95% CI, 21.6-∞), exceeding survival using recursive partitioning analysis and matched historical controls. Four patients remained progression-free at 59 to 64 months from diagnosis. No known prognostic factors [age, Karnofsky performance status (KPS), mutation, and promoter methylation] predicted more favorable outcomes for the patients in this cohort. Despite increased Treg proportions following DI-TMZ, patients receiving pp65-DCs showed long-term PFS and OS, confirming prior studies targeting cytomegalovirus in glioblastoma. .