Details

Autor(en) / Beteiligte

• Ahmed, Nabil
• Brawley, Vita
• Hegde, Meenakshi
• Bielamowicz, Kevin
• Kalra, Mamta
• Landi, Daniel
• Robertson, Catherine
• Gray, Tara L
• Diouf, Oumar
• Wakefield, Amanda
• Ghazi, Alexia
• Gerken, Claudia
• Yi, Zhongzhen
• Ashoori, Aidin
• Wu, Meng-Fen
• Liu, Hao
• Rooney, Cliona
• Dotti, Gianpietro
• Gee, Adrian
• Su, Jack
• Kew, Yvonne
• Baskin, David
• Zhang, Yi Jonathan
• New, Pamela
• Grilley, Bambi
• Stojakovic, Milica
• Hicks, John
• Powell, Suzanne Z
• Brenner, Malcolm K
• Heslop, Helen E
• Grossman, Robert
• Wels, Winfried S
• Gottschalk, Stephen

Titel

HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial

Ist Teil von

• JAMA oncology, 2017-08, Vol.3 (8), p.1094

Ort / Verlag

United States

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was 10 weeks to 29 months (median, 8 months). Monotherapy with autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs with a CD28.ζ-signaling endodomain (HER2-CAR VSTs). Primary end points were feasibility and safety. The key secondary end points were T-cell persistence and their antiglioblastoma activity. A total of 17 patients (8 females and 9 males; 10 patients ≥18 years [median age, 60 years; range, 30-69 years] and 7 patients <18 years [median age, 14 years; range, 10-17 years]) with progressive HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR VSTs (1 × 106/m2 to 1 × 108/m2) without prior lymphodepletion. Infusions were well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected in the peripheral blood for up to 12 months after the infusion by quantitative real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7 children), 1 had a partial response for more than 9 months, 7 had stable disease for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients with stable disease are alive without any evidence of progression during 24 to 29 months of follow-up. For the entire study cohort, median overall survival was 11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5 months (95% CI, 17.2-34.6 months) from diagnosis. Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical benefit for patients with progressive glioblastoma. Further evaluation of HER2-CAR VSTs in a phase 2b study is warranted as a single agent or in combination with other immunomodulatory approaches for glioblastoma.