Autologous t-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma

Schuessler, Andrea, Smith, Corey, Beagley, Leone, Boyle, Glen M., Rehan, Sweera, Matthews, Katherine, Jones, Linda, Crough, Tania, Dasari, Vijayendra, Klein, Kerenaftali, Smalley, Amy, Alexander, Hamish, Walker, David G. and Khanna, Rajiv (2014) Autologous t-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Research, 74 13: 3466-3476. doi:10.1158/0008-5472.CAN-14-0296

Author Schuessler, Andrea
Smith, Corey
Beagley, Leone
Boyle, Glen M.
Rehan, Sweera
Matthews, Katherine
Jones, Linda
Crough, Tania
Dasari, Vijayendra
Klein, Kerenaftali
Smalley, Amy
Alexander, Hamish
Walker, David G.
Khanna, Rajiv
Title Autologous t-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma
Journal name Cancer Research   Check publisher's open access policy
ISSN 1538-7445
Publication date 2014-07-01
Year available 2014
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-14-0296
Open Access Status Not yet assessed
Volume 74
Issue 13
Start page 3466
End page 3476
Total pages 11
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Abstract Glioblastoma multiforme (GBM) is one of the most aggressive human brain malignancies. Even with optimal treatment, median survival is less than 6 months for patients with recurrent GBM. Immune-based therapies have the potential to improve patient outcome by supplementing standard treatment. Expression of human cytomegalovirus (CMV) antigens in GBM tissues provides the unique opportunity to target viral antigens for GBM therapy. Here, we report findings of a formal clinical assessment of safety and potential clinical efficacy of autologous CMV-specific T-cell therapy as a consolidative treatment for recurrent GBM. From a total of 19 patients with recurrent GBM, CMV-specific T cells were successfully expanded from 13 patients (68.4%), 11 of whom received up to four T-cell infusions. Combination therapy based on T-cell infusion and chemotherapy was well tolerated, and we detected only minor adverse events. The overall survival of these patients since first recurrence ranged from 133 to 2,428 days, with a median overall survival of 403 days. Most importantly, 4 of 10 patients that completed the treatment remained progression free during the study period. Furthermore, molecular profiling of CMV-specific T-cell therapy from these patients revealed distinct gene expression signatures, which correlated with their clinical response. Our study suggests that a combination therapy with autologous CMV-specific T cells and chemotherapy is a safe novel treatment option and may offer clinical benefit for patients with recurrent GBM. Cancer Res; 74(13); 3466-76.
Keyword Oncology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1020325
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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