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Reduced efficacy of multiple doses of CpG-matured dendritic cell tumor vaccine in an experimental model
Authors:Pourgholaminejad Arash  Jamali Arezoo  Samadi-Foroushani Morteza  Amari Afshin  Mirzaei Reza  Ansaripour Bita  Khansari Nemat  Aghasadeghi Mohammad Reza  Baban Babak  Hadjati Jamshid
Institution:aDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;bDepartment of Laboratory Sciences, School of Paramedicine, Tehran University of Medical Sciences, Tehran, Iran;cDepartment of Immunology, Shaheed Sadughi University of Medical Sciences, Yazd, Iran;dDepartment of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;eDepartment of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran;fImmunotherapy Center and Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA
Abstract:CpG motifs have been advanced as agents that stimulate the maturation of DCs for immunotherapy. The present study tested the hypothesis that multiple doses of CpG-matured DC vaccine would be efficacious for complete eradication of experimentally-induced tumor. Accordingly, WEHI164 cells were implanted subcutaneously in the flank of BALB/c mice. During DC culture, tumor lysate was added to immature DCs followed by addition of CpG or non-CpG control 4–6 h later. A total of three doses of CpG or non-CpG control-matured DCs were injected around tumors. The results showed that multiple doses of CpG-matured DCs led to considerable decrease in cytotoxicity of lymphocytes and significantly increased tumor growth rate compared to a single dose. Further, mice which received three doses of the vaccine also displayed significant FoxP3 in tumor tissue. In conclusion, multiple doses of CpG-matured DCs exhibited decreased anti-tumor immunity in association with increased expression of FoxP3.
Keywords:Cell therapy  FoxP3  Synthetic oligodeoxynucleotides  Tumor immunotherapy
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