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Abstract(Please copy/paste the abstract send to the congress) : |
Synergistic effect of combined local irradiation and dendritic cell vaccine in murine fibrosarcoma tumor
Author Block A. Jamali1, A. Amari2, A. Pourgholaminejad2, A. Saei3, R. Boghozian3, Z. Gheflati3, N. Sepanlou4, J. Hadjati3;
1School of Allied Medical Siences-Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of, 2Tarbiat Modarres University, Tehran, Iran, Islamic Republic of, 3School of Medicine -Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of, 4School of Medicine -Imam Khomeini Hospital, Tehran, Iran, Islamic Republic of.
Abstract:
Objective: Neither radiotherapy alone nor dendritic cell (DCs) vaccination can successfully eradicate the tumor. Radiation induces tumor cells apoptosis, resulting in tumor antigens and danger signals releasing which are favorable for DC capturing antigens. Hence,combined irradiation and activated DC vaccine may be a novel strategy for treating solid tumors.
Methods: WEHI-164 a Balb/c derived fibrosarcoma cells were injected subcutaneously (SC) to female Balb/c mice. Bone marrow cells were cultured with GM-CSF and IL-4 for 5 days, Followed by adding Listeria monocytogenes antigens and tumor cell lysate for another 2 days. 7 days after tumor challenge, localized single dose (10 Gy) irradiation was applied. Activated DCs were injected SC around the tumor site, the day after irradiation. Tumor size was monitored every other day. Two weeks after immunization cytotoxic activity of splenocytes was measured with a LDH cytotoxicity detection kit. Intercellular INF_γ assessment was performed using a FACScalibur cytometer with WinMDI2.9 software.
Results: Immunotherapy with activated DCs after irradiation has a potent cellular response. The cytotoxicity of splenocytes in combined therapy specially which received complete cocktail was more than other groups (P< 0.016). Evaluation of intra-cellular INF-γ staining showed significant increase in animal which had received combined therapy (P<0.001).
Tumor size monitoring and mice survival showed reduced tumor size and increased survival in group which received both treatment (P=0.011, P <0.001).
Conclusion: Combination therapy using activated Listeria monocytogenes DCs and local irradiation induced noticeable efficient cellular antitumor response against poorly immunogenic tumor as well as tumor regression. |