1611P - The combination of antitumor vaccine and low doses of doxorubicin as an effective method against tumor immunosuppression

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cytotoxic agents
Immunotherapy
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological therapy
Presenter Oleksandr Gorbach
Citation Annals of Oncology (2014) 25 (suppl_4): iv546-iv563. 10.1093/annonc/mdu358
Authors O. Gorbach1, N. Khranovska1, O. Skachkova1, R. Sydor1, N. Svergun1, V. Pozur2
  • 1Laboratory Of Experimental Oncology, National Cancer Institute of the MPH Ukraine, 03022 - Kiev/UA
  • 2Educational And Scientific Centre «institute Of Biology», Kyiv National Taras Shevchenko University, 01601 - Kiev/UA

Abstract

Aim

Combined therapy based on dendritic cells (DC) and low-dose chemotherapy is being intensively investigated worldwide. The using of low-dose chemotherapy, such as cyclophosphamide, reduces the number of T-regulatory cells, which in turn decreases the suppression of the immune system of cancer patients. The aim: to investigate the influence of combined immunotherapy on T-regulatory component of the immune system in murine sarcoma-37 model.

Methods

In experimental investigation 120 CBA mice have been involved. Sarcoma-37 was injected intramuscularly at lethal dose (2*106 cells per animal). Doxorubicin was injected intraperitoneally 5 times in metronomic regimen according to the two schemes: 0.2mg/kg or 2 mg/kg on the 7th day after tumor transplantation with interval of 1 day and 3 days, respectively. DC vaccines were administered intravenously 3 times on day 4 after the chemotherapy in 3 day interval.

Results

We have found that both of the proposed chemoimmunotherapy schemes had a significant antitumor and immunomodulating effect. Significant decreasing of primary tumor volume in both animal groups which received combined therapy compared with the control has been found (p<0.01). We have shown that administration of DC vaccine and doxorubicin at a concentration of 0.2 mg/kg decrease FoxP3 mRNA expression level in spleen cells in 1.7 times (р=0.03) compared with the control group. Moreover, the administration of this combined therapy decrease dTGF-ß mRNA expression level in spleen cells by 1.8 times (р=0.028) compared with the control group. This data has shown that the chemoimmunotherapy decreases the T-regulatory cells suppressive effect on the animal's immune system.

Conclusions

Low-dose chemotherapeutics decrease the tumor suppression on immune system and enhance the antitumor effect of DC-based immunotherapy. These investigations form the basis to a new multimodality treatment in cancer patients.

Disclosure

All authors have declared no conflicts of interest.