Epstein-Barr virus-targeted immunotherapy for nasopharyngeal carcinoma

Masmoudi, Amine; Toumi, Nabil; Khanfir, Afef; Kallel-Slimi, Lamia; Daoud, J.; Karray, H.; Frikha, M.

doi:10.1016/j.ctrv.2007.04.007

Cited by 35 publications

(17 citation statements)

References 37 publications

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“…It is possible that NACT followed by CCRT is not effective enough to eradicate micrometastases in this group of patients, therefore, the inclusion of adjuvant chemotherapy may be necessary. Secondly, the EBV viral antigens expressed by NPC tumor cells have become attractive targets for immunotherapy as another form of targeted therapy in this era of personalized management 18-19. Adoptive immunotherapy is a potential avenue for patients in the high-risk group.…”

Section: Discussionmentioning

confidence: 99%

Is pretreatment Epstein-Barr virus DNA still associated with 6-year survival outcomes in locoregionally advanced nasopharyngeal carcinoma?

Jin¹,

Yao²,

Zhang³

et al. 2017

J. Cancer

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Purpose: The objective of this study was to confirm the association between pretreatment Epstein-Barr virus (EBV) DNA (pre-DNA) load and survival outcomes after long-term follow-up in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Materials and Methods: Between November 2009 and February 2012, a total of 1036 patients with LA-NPC were enrolled. There were 762 patients in stage III and 274 in stage IVA-B. All patients were treated with radical radiotherapy with or without chemotherapy, and pre-DNA concentrations were quantified by a polymerase chain reaction assay. Patient outcomes were evaluated.Results: The 5-year overall survival (OS), distant metastasis-free surviva (DMFS), locoregional relapse-free survival (LRFS), and progression-free survival (PFS) rates were 84.7%, 87.0%, 90.2%, and 77.1%, respectively. By using previously defined pre-DNA cutoff value (1500 copies/ml pretreatment), pre-DNA was an independent prognostic predictor for OS, DMFS, and PFS using log-rank test. Multivariate Cox analysis also confirmed these results. Subgroup analysis indicated that the 5-year OS, DMFS, and PFS rates in patients staged IVA-B with pre-DNA < 1500 copies/ml were similar to those patients staged III with pre-DNA ≥ 1500 copies/ml, whereas patients staged IVA-B patients with pre-DNA ≥ 1500 copies/ml predicted worse outcome.Conclusions: In this expanded study, the prognostic significance of pre-DNA was confirmed using predefined cutoff value in an independent patient group, and pre-DNA was identified as an independent prognostic marker for the risk stratification in LA-NPC.

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Section: Discussionmentioning

confidence: 99%

Is pretreatment Epstein-Barr virus DNA still associated with 6-year survival outcomes in locoregionally advanced nasopharyngeal carcinoma?

Jin¹,

Yao²,

Zhang³

et al. 2017

J. Cancer

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“…Thus, treatment innovations with immunotherapy are currently being assessed to improve outcomes. The Epstein-Barr virus-specific cytotoxic T lymphocyte (CTL) and dendritic cell-based therapies have been demonstrated to be well tolerated [5]. However, clinical benefits have been demonstrated in some patients only.…”

Section: Introductionmentioning

confidence: 99%

Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced ζ-chain expression in nasopharyngeal carcinoma patients

Yip

Abdullah

Yusoff

et al. 2009

Clinical and Experimental Immunology

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SummaryThe pathological significance of the mechanisms of tumour immune-evasion and/or immunosuppression, such as loss of T cell signalling and increase in regulatory T cells (Tregs), has not been well established in the nasopharyngeal carcinoma (NPC) microenvironment. To evaluate the Treg immunophenotypes in tumour-infiltrating lymphocytes (TILs), we performed a doubleenzymatic immunostaining for detection of forkhead box P3 (FoxP3) and other markers including CD4, CD8, and CD25 on 64 NPC and 36 nonmalignant nasopharyngeal (NP) paraffin-embedded tissues. Expression of CD3z and CD3e was also determined. The prevalence of CD4 + FoxP3 + cells in CD4 + T cells and the ratio of FoxP3 + /CD8 + were increased significantly in NPC compared with those in NP tissues (P < 0·001 and P = 0·025 respectively). Moreover, the ratio of FoxP3 NPC was significantly lower than that in NP tissues (P = 0·005), suggesting an imbalance favouring activated phenotype of T cells in NPC. A significant negative correlation between the abundance of FoxP3+ and CD25 + FoxP3 -cells (P < 0·001) was also identified. When histological types of NPC were considered, a lower ratio of FoxP3 + /CD25 + FoxP3 -was found in non-keratinizing and undifferentiated carcinomas. Increased CD4 + FoxP3 + /CD4 + proportion and FoxP3 + /CD8 + ratio were associated with keratinizing squamous cell carcinoma. A reduced expression of CD3z in TILs was found in 20·6% of the NPC tissues but none of the NP tissues. These data provide evidence for the imbalances of Treg and effector T cell phenotypes and down-regulation of signal-transducing molecules in TILs, supporting their role in suppression of immune response and immune evasion of NPC.

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“…Epstein-Barr virus (EBV) is present in virtually all poorly differentiated and undifferentiated nonkeratinizing NPC (WHO type II and III). Consequently, the viral antigens expressed by the tumor cells are attractive targets for immunotherapy and may be a potential avenue for the development of new therapies for the treatment of NPC (6,7).…”

Section: Introductionmentioning

confidence: 99%

Effective Treatment of Metastatic Forms of Epstein-Barr Virus–Associated Nasopharyngeal Carcinoma with a Novel Adenovirus-Based Adoptive Immunotherapy

et al. 2012

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Nasopharyngeal carcinoma (NPC) is endemic in China and Southeast Asia where it is tightly associated with infections by Epstein-Barr virus (EBV). The role of tumor-associated viral antigens in NPC renders it an appealing candidate for cellular immunotherapy. In earlier preclinical studies, a novel adenoviral vector-based vaccine termed AdE1-LMPpoly has been generated that encodes EBV nuclear antigen-1 (EBNA1) fused to multiple CD8 þ T-cell epitopes from the EBV latent membrane proteins, LMP1 and LMP2. Here, we report the findings of a formal clinical assessment of AdE1-LMPpoly as an immunotherapeutic tool for EBV-associated recurrent and metastatic NPC. From a total of 24 patients with NPC, EBV-specific T cells were successfully expanded from 16 patients with NPC (72.7%), whereas six patients with NPC (27.3%) showed minimal or no expansion of virus-specific T cells. Transient increase in the frequencies of LMP1&2-and EBNA1-specific T-cell responses was observed after adoptive transfer to be associated with grade I flu-like symptoms and malaise. The time to progression in these patients ranged from 38 to 420 days with a mean time to progression of 136 days. Compared with patients who did not receive T cells, the median overall survival increased from 220 to 523 days. Taken together, our findings show that adoptive immunotherapy with AdE1-LMPpoly vaccine is safe and well tolerated and may offer clinical benefit to patients with NPC. Cancer Res; 72(5); 1116-25. Ó2012 AACR.

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Epstein-Barr virus-targeted immunotherapy for nasopharyngeal carcinoma

Cited by 35 publications

References 37 publications

Is pretreatment Epstein-Barr virus DNA still associated with 6-year survival outcomes in locoregionally advanced nasopharyngeal carcinoma?

Is pretreatment Epstein-Barr virus DNA still associated with 6-year survival outcomes in locoregionally advanced nasopharyngeal carcinoma?

Increase in tumour-infiltrating lymphocytes with regulatory T cell immunophenotypes and reduced ζ-chain expression in nasopharyngeal carcinoma patients

Effective Treatment of Metastatic Forms of Epstein-Barr Virus–Associated Nasopharyngeal Carcinoma with a Novel Adenovirus-Based Adoptive Immunotherapy

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