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Mol Ther. 2014 Jan;22(1):132-9. doi: 10.1038/mt.2013.242. Epub 2013 Oct 17.

Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma.

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Division of Medical Oncology, National Cancer Centre, Singapore.
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
Division of Clinical Trials and Epidemiological Research, National Cancer Centre, Singapore.
Duke-NUS Graduate Medical School, Singapore.
Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.


The outcomes for patients with metastatic or locally recurrent Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) remain poor. Adoptive immunotherapy with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) has proven clinical efficacy, but it has never been evaluated in the first-line treatment setting in combination with chemotherapy. To evaluate the safety and efficacy of a chemotherapy in combination with adoptive EBV-CTL transfer, we conducted a phase 2 clinical trial consisting of four cycles of gemcitabine and carboplatin (GC) followed by up to six doses of EBV-CTL. Thirty-eight patients were enrolled, and 35 received GC and EBV-CTL. GC-CTL therapy resulted in a response rate of 71.4% with 3 complete responses and 22 partial responses. With a median follow up of 29.9 months, the 2-year and 3-year overall survival (OS) rate was 62.9 and 37.1%, respectively. Five patients did not require further chemotherapy for more than 34 months since initiation of CTL. Infusion of CTL products containing T cells specific for LMP2 positively correlated with OS (hazard ratio: 0.35; 95% confidence interval: 0.14-0.84; P = 0.014). Our study achieved one of the best survival outcomes in patients with advanced NPC, setting the stage for a future randomized study of chemotherapy with and without EBV-CTL.

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