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Optimization of LMP‐specific CTL expansion for potential adoptive immunotherapy in NPC patients
Author(s) -
Lutzky Viviana P,
Davis Joanne E,
Crooks Pauline,
Corban Monika,
Smith Mark C,
Elliott Michael,
Morrison Leanne,
Cross Simone,
Tscharke David,
Panizza Benedict,
Coman William,
Bharadwaj Mandvi,
Moss Denis J
Publication year - 2009
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.25
Subject(s) - ctl* , cytotoxic t cell , immunotherapy , immunology , antigen , lymphoblast , biology , cancer research , adoptive cell transfer , immune system , virology , t cell , cd8 , in vitro , cell culture , biochemistry , genetics
Nasopharyngeal carcinoma (NPC) is Epstein–Barr virus (EBV) positive in all undifferentiated cases, expressing the latency II phenotype of latent membrane proteins (LMPs) 1 and 2, in addition to EBV nuclear antigen (EBNA) 1. Several studies have attempted to treat NPC with EBV‐specific cytotoxic T lymphocyte (CTL) with a partial response. To improve this therapy, there is a need to expand CTL targeted to the latency II antigens of EBV, rather than the immunodominant EBV nuclear antigens 3–6 peptides typically expanded by lymphoblastoid cells. In order to maximize the expansion of LMP‐specific CTL in vitro for use in adoptive immunotherapy of nasopharyngeal carcinoma patients, we used lymphoblastoid cell lines coated with synthetic peptides corresponding to CTL determinants from the LMP proteins. We investigated several issues pertaining to the expansion of an immunologically weak CTL response, including peptide and interleukin‐2 concentration, and screening assays for selecting the optimal peptide for use in expansion of LMP‐specific CTL. Although screening of ex vivo peripheral blood mononuclear cells did not prove to be useful in the selection of an LMP peptide for use in CTL cultures, the peptide and interleukin‐2 concentrations were critical for the maximum expansion of CTL. Therefore, it is imperative that stimulation protocols are optimized for the expansion of LMP‐specific CTL.