Journal
MOLECULAR THERAPY
Volume 29, Issue 2, Pages 734-743Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2020.09.040
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Funding
- Institute of Molecular and Cell Biology (IMCB) Colab Tessa Therapeutics [IAF ICP I1601E0006]
- Cell Therapy Programme [IAF-PP H18/01/a0/022]
- National Medical Research Council (NMRC) ClinicianScientist Individual Research Grant (CS-IRG) [NMRC/CIRG/1352/2013]
- Clinician Scientist Award Senior Investigator (CSA-SI) [NMRC/CSASI/0013/2017]
- Open FundLarge Collaborative Grant (OF-LCG) [NMRC/OFLCG/003/2018]
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Late-stage EBV-positive NPC poses a challenge in treatment, but a combination of chemotherapy and EBVST immunotherapy has shown promising response rates. Analysis of EBV DNA plasma concentrations and peripheral monocyte levels can help predict overall survival in patients.
Advanced, late-stage Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) is incurable, and its treatment remains a clinical and therapeutic challenge. Results from a phase II clinical trial in advanced NPC patients employing a combined chemotherapy and EBV-specific T cell (EBVST) immunotherapy regimen showed a response rate of 71.4%. Longitudinal analysis of patient samples showed that an increase in EBV DNA plasma concentrations and the peripheral monocyte-to-lymphocyte ratio negatively correlated with overall survival. These parameters were combined into a multivariate analysis to stratify patients according to risk of death. Immunophenotyping at serial time points showed that low-risk individuals displayed significantly decreased amounts of monocytic myeloid-derived suppressor cells postchemotherapy, which subsequently influenced successful cytotoxic T-lymphocyte (CTL) immunotherapy. Examination of the low-risk group, 2 weeks post-EBVST infusion, showed that individuals with a greater overall survival possessed an increased frequency of CD8 central and effector memory T cells, together with higher levels of plasma interferon (IFN)-gamma, and cytotoxic lymphocyte-associated transcripts. These results highlight the importance of the rational selection of chemotherapeutic agents and consideration of their impact on both systemic immune responses and downstream cellular immunotherapy outcomes.
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