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.
Masoumeh Khamisabadi; Samaneh Arab; Masoumeh Motamedi; Nematollah khansari; Seied Mohammad Moazzeni; Zahra Gheflati; Jamshid Hadjati
Volume 5, Issue 1 , March 2008, , Pages 36-44
Abstract
Background: The use of dendritic cells (DCs) as a cellular adjuvant provides a promis-ing approach in immunotherapy of cancer. It has been demonstrated that Listeria mono-cytogenes activated DCs pulsed ex vivo with tumor antigens trigger a systemic Th1-biased specific immune response and a single dose ...
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Background: The use of dendritic cells (DCs) as a cellular adjuvant provides a promis-ing approach in immunotherapy of cancer. It has been demonstrated that Listeria mono-cytogenes activated DCs pulsed ex vivo with tumor antigens trigger a systemic Th1-biased specific immune response and a single dose of this vaccine will cause a consider-able anti tumor immunity. Objective: The present study was designed to evaluate the ability of multiple doses of tumor antigen-pulsed DCs, matured in the presence of Lis-teria monocytogenes components in induction of a potent anti-tumor response and the prevention of tumor formation in an experimental model. Methods: Bone-marrow de-rived DCs (BMDCs) were cultured in the presence of GM-CSF and IL-4. After 5 days, tumor lysates with/without Listeria monocytogenes lysate were added to the culture media for another 2 days. Mice received mature and tumor antigen pulsed dendritic cells subcutaneously in 3 groups. Tumor growth was monitored and two weeks after immu-notherapy, cytotoxic activity of CD8+ T cells was evaluated in different groups. Re-sults: According to the findings, repeated doses of vaccine did not lead to a significant increase in the activity of cytotoxic T cells and decreased tumor growth of immunized animals. Conclusion: The current study suggests that increased doses of vaccine do not have sufficient efficiency for prevention of tumor induction. Generation of T regulatory responses upon repeated doses of such vaccines should be considered in future investi-gations.
