title: Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response.
abstract: Adoptive T cell therapy has emerged as a powerful strategy to treat human cancers especially haematological malignancies. Extension of these therapies to solid cancers remains a significant challenge especially in the context of defining immunological correlates of clinical responses. Here we describe results from a clinical study investigating autologous Epstein-Barr virus (EBV)-specific T cells generated using a novel AdE1-LMPpoly vector to treat patients with nasopharyngeal carcinoma (NPC) either pre-emptively in at-risk patients with no or minimal residual disease (N/MRD) or therapeutically in patients with active recurrent/metastatic disease (ARMD). Tolerability, safety and efficacy, including progression-free survival (PFS) and overall survival (OS), were evaluated following adoptive T-cell immunotherapy. Twenty-nine patients, including 20 with ARMD and nine with N/MRD, successfully completed T-cell therapy. After a median follow-up of 18.5 months, the median PFS was 5.5 months (95% CI 2.1 to 9.0 months) and the median OS was 38.1 months (95% CI 17.2 months to not reached). Post-immunotherapy analyses revealed that disease stabilization in ARMD patients was significantly associated with the functional and phenotypic composition ofin vitro-expanded T cell immunotherapy. These included a higher proportion of effector CD8+T-cells and an increased number of EBV-specific T-cells with broader antigen specificity. These observations indicate that adoptive immunotherapy with AdE1-LMPpoly-expanded T cells stabilizes relapsed, refractory NPC without significant toxicity. Promising clinical outcomes in N/MRD patients further suggest a potential role for this approach as a consolidation treatment following first-line chemotherapy.
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong , Hong Kong.
authors.forename: Victor
authors.initials: V
authors.lastname: Lee
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schuessler
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Leone
authors.initials: L
authors.lastname: Beagley
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Sweera
authors.initials: S
authors.lastname: Rehan
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong , Hong Kong.
authors.forename: Janice
authors.initials: J
authors.lastname: Tsang
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong , Hong Kong.
authors.forename: Vivian
authors.initials: V
authors.lastname: Li
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong , Hong Kong.
authors.forename: Randal
authors.initials: R
authors.lastname: Tiu
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Neller
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthews
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine , Cardiff, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Burrows
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Glen M
authors.initials: GM
authors.lastname: Boyle
authors.affiliation: Comprehensive Oncology Centre, Hong Kong Sanatorium Hospital , Hong Kong.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Princess Alexandra Hospital, University of Queensland , Brisbane, Queensland, Australia.
authors.forename: Benedict
authors.initials: B
authors.lastname: Panizza
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Princess Alexandra Hospital, University of Queensland , Brisbane, Queensland, Australia.
authors.forename: Sandro V
authors.initials: SV
authors.lastname: Porceddu
authors.affiliation: Department of Pathology, Queen Mary Hospital, The University of Hong Kong , Hong Kong.
authors.forename: John
authors.initials: J
authors.lastname: Nicholls
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, The University of Hong Kong , Hong Kong.
authors.forename: Dora
authors.initials: D
authors.lastname: Kwong
authors.affiliation: QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute , Brisbane, Queensland, Australia.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
keywords: Adoptive immunotherapy; Epstein-Barr virus; T cells; nasopharyngeal carcinoma; safety