Format

Send to

Choose Destination
Cancer Res. 2014 Jul 1;74(13):3466-76. doi: 10.1158/0008-5472.CAN-14-0296. Epub 2014 May 4.

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

Author information

1
Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
2
Cancer Drug Mechanisms Group;
3
Statistics Unit, QIMR Berghofer Medical Research Institute; and.
4
Newro Foundation, The Wesley Hospital, Brisbane, Queensland, Australia.
5
Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory; Newro Foundation, The Wesley Hospital, Brisbane, Queensland, Australia.
6
Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory; rajiv.khanna@qimr.edu.au.

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.

PMID:
24795429
DOI:
10.1158/0008-5472.CAN-14-0296
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center