Format

Send to

Choose Destination
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.

Author information

1
Division of Medical Oncology, National Cancer Centre, Singapore.
2
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
3
Division of Clinical Trials and Epidemiological Research, National Cancer Centre, Singapore.
4
Duke-NUS Graduate Medical School, Singapore.
5
Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.

Abstract

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.

PMID:
24297049
PMCID:
PMC3978790
DOI:
10.1038/mt.2013.242
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center