title: Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma.
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.
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Andrea
authors.initials: A
authors.lastname: Schuessler
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Leone
authors.initials: L
authors.lastname: Beagley
authors.affiliation: Cancer Drug Mechanisms Group;
authors.forename: Glen M
authors.initials: GM
authors.lastname: Boyle
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Sweera
authors.initials: S
authors.lastname: Rehan
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Katherine
authors.initials: K
authors.lastname: Matthews
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Linda
authors.initials: L
authors.lastname: Jones
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Tania
authors.initials: T
authors.lastname: Crough
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory;
authors.forename: Vijayendra
authors.initials: V
authors.lastname: Dasari
authors.affiliation: Statistics Unit, QIMR Berghofer Medical Research Institute; and.
authors.forename: Kerenaftali
authors.initials: K
authors.lastname: Klein
authors.affiliation: Newro Foundation, The Wesley Hospital, Brisbane, Queensland, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Smalley
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory; Newro Foundation, The Wesley Hospital, Brisbane, Queensland, Australia.
authors.forename: Hamish
authors.initials: H
authors.lastname: Alexander
authors.affiliation: Newro Foundation, The Wesley Hospital, Brisbane, Queensland, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Walker
authors.affiliation: Authors' Affiliations: QIMR Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory; rajiv.khanna@qimr.edu.au.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy; D003587:Cytomegalovirus / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D005909:Glioblastoma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation*; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods; D055815:Young Adult
chemical_list: D000956:Antigens, Viral