title: The efficacy of a novel vaccine approach using tumor cells that ectopically express a codon-optimized murine GM-CSF in a murine tumor model.
abstract: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a potent immunomodulatory cytokine that is known to facilitate vaccine efficacy by promoting the development and prolongation of both humoral and cellular immunity. Here, we investigated a novel vaccine approach using a human papillomavirus (HPV)-16 E6/E7-transformed cell line, TC-1, that ectopically expresses a codon-optimized 26-11-2015 murine GM-CSF (cGM-CSF). Ectopically expressing cGM-CSF in TC-1 (TC-1/cGM) cells significantly increased expression of a GM-CSF that was functionally identical to wt GM-CSF by 9-fold compared with ectopically expressed wild type GM-CSF in TC-1 cells (TC-1/wt). Mice vaccinated with irradiated TC-1/cGM cells exhibited enhanced survival compared with mice vaccinated with TC-1/wt cells when both groups were subsequently injected with live TC-1. Consistently, mice vaccinated with irradiated TC-1/cGM cells exhibited stronger IFN-γ production in HPV E7-specific CD8(+) T cells. More dendritic cells were recruited to the draining lymph nodes (dLNs) of mice vaccinated with TC-1/cGM cells than C-1/wt cells. Regarding dLN cell recall responses, both proliferation and IFN-γ production in the HPV E7-specific CD8(+) T cells were enhanced in mice that were vaccinated with TC-1/cGM cells. Our results demonstrate that a novel practical molecular strategy utilizing a codon-optimized GM-CSF gene overcomes the limitation and improves the efficacy of tumor cell-based vaccines.
authors.affiliation: Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Chu-Chi
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Ching-Chou
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Jan-Mou
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Fang
authors.affiliation: Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Kuo-Shian
authors.initials: KS
authors.lastname: Chang
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Kwong-Kwok
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Cheng-Tao
authors.initials: CT
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. Electronic address: jtqiu@adm.cgmh.org.tw.
authors.forename: Jiantai Timothy
authors.initials: JT
authors.lastname: Qiu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016019:Survival Analysis
chemical_list: D019496:Cancer Vaccines; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Cancer; Cytotoxic T cells; Vaccine; cGM-CSF