Gorbach O. Antitumor efficacy of vaccinotherapy based on dendritic cells in combination with chemotherapy in the experiment

The thesis was dedicated to investigate the antitumor and immunomodulatory efficacy of DC-vaccine in combination with low-dose cyclophosphamide, doxorubicin and cisplatin in murine tumor models. The immunotherapy based on the DC vaccine and low-dose chemotherapy was first combined for antitumor therapy in this study. Combined therapy based on DC-vaccine and low-dose cyclophosphamide, doxorubicin and cisplatin had significant antitumor effect in animals with transplanted Lewis lung carcinoma and sarcoma-37. We had found that combined therapy based on the DC-vaccine and doxorubicin at a total dose of 1 mg/kg or DC-vaccine and cisplatin at a total dose of 10 mg/kg had decreased VEGF and TGF-beta mRNA expression levels in tumor tissue. This may indicate the anti-angiogenic effect of treatment and weakening of local immunosuppression. It was determined that doxorubicin at a total dose of 1 mg/kg or cisplatin at a total dose of 10 mg/kg with DC-vaccine reduced systemic immunosuppression and enhanced IFN-gamma mRNA expression of spleen cells. For animals treated with cyclophosphamide at a total dose of 8 mg/kg and the DC-vaccine was identified weakening of systemic immunosuppression and, probably, switch to the cellular immune response by decrease of TGF-beta, IL-10, IL-4 mRNA expression levels. It was established that escalation of chemotherapy dose did not increase efficiency of chemoimmunotherapy. The most optimal schemes of combined therapy were DC-vaccine and cyclophosphamide at a total dose of 8 mg/kg, DC vaccine and doxorubicin at a total dose of 1 mg/kg or DC-vaccine and cisplatin at a total dose 10 mg/kg.