Bahareh Zand; Samaneh Arab; Nasim Kheshtchin; Abazar Arabameri; Mahboubeh Ashourpour; Davoud Asemani; Ehsan Sharif-Paghaleh; Farshid Noorbakhsh; Jamshid Hadjati
Abstract
Background: Mathematical modeling offers the possibility to select the optimal dose of a drug or vaccine. Considerable evidence show that many bacterial components can activate dendritic cells (DCs). Our previous report showed that multiple doses of DCs matured with Listeria monocytogenes led to tumor ...
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Background: Mathematical modeling offers the possibility to select the optimal dose of a drug or vaccine. Considerable evidence show that many bacterial components can activate dendritic cells (DCs). Our previous report showed that multiple doses of DCs matured with Listeria monocytogenes led to tumor regression whereas multiple doses of CpG-matured DCs affected tumor reversely. Objective: To assess a combined pattern of DC vaccination proposed by a mathematical model for tumor regression. Method: WEHI164 cells were inoculated subcutaneously in the right flank of BALB/c mice. Bone marrow-derived DCs were matured by Listeria monocytogenes and CpG motifs. DCs were injected using specific patterns and doses predicted by mathematical modeling. Effector cell-mediated cytotoxicity, gene expression of T cell-related transcription factors, as well as tumor growth and survival rate, were assessed in different groups. Results: Our study indicated that the proposed mathematical model could simulate the tumor and immune system interaction, and it was verified by decreasing tumor size in the List+CpG group. However, comparing the effect of different treatment modalities on Th1/Treg transcription factor expression or cytotoxic responses revealed no advantage for combined therapy over other treatment modalities. Conclusions: These results suggest that finding new combinations of DC vaccines for the treatment of tumors will be promising in the future. The results of this study support the mathematical modelling for DC vaccine design. However, some parameters in this model must be modified to provide a more optimized therapy approach.
Saeid Abediankenari; Yousef Yousedzadeh; Hossein Azadeh; Mohammad Vahedi
Volume 7, Issue 2 , June 2010, , Pages 83-87
Abstract
Background: Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. Objective: In this study, we compared tumor necrosis ...
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Background: Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. Objective: In this study, we compared tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG oligonucleotides in inducing dendritic cell maturation. Methods: We generated immature dendritic cells with GM-CSF in combination with IL-4 from peripheral blood mononuclear adherent cells and used tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG for the induction of dendritic cell maturation. CD83 maturation marker on the dendritic cells was analyzed by flowcytometry after 7 days. In addition, mixed leukocyte reaction between dendritic cells and T cells was performed by MTT proliferation assay. Results: Flow cytometry results demonstrated a comparable high level of CD83 expression on the mature dendritic cells generated by TNF-α, CpG, Poly I:C, and LPS treatment of the immature dendritic cells. However, a significantly poorer proliferation of lymphocytes cocultured with the Poly I:C-treated DCs was observed compared to the CpG-treated DCs in mixed leukocyte reaction (p=0.026). Conversely, a significantly stronger proliferation of lymphocytes was observed when cocultured with TNF-α-treated DCs compared to the LPS-treated DCs (p=0.025). Conclusion: Our results indicated that all of studied maturation inducing factors can be used in DC maturation but TNF-α and CpG were the preferred in vitro maturation factors. It is concluded that maturation of dendritic cells by CpG motif and TNF-α can be used to regulate immune responses.