9P - Low doses of cisplatin can help dendritic cell vaccines to reduce immunosuppression in tumor microenvironment

Date 21 November 2014
Event ESMO Symposium on Immuno-Oncology 2014
Session Welcome reception and Poster viewing
Topics Anti-Cancer Agents & Biologic Therapy
Cancer Immunology and Immunotherapy
Presenter Oleksandr Gorbach
Authors O. Gorbach1, N. Khranovska2, O. Skachkova2, R. Sydor2, N. Svergun2, V. Pozur1
  • 1Educational And Scientific Centre Institute Of Biology, Kyiv National Taras Shevchenko University, 01601 - Kiev/UA
  • 2Laboratory Of Experimental Oncology, National Cancer Institute of the MPH Ukraine, 03022 - Kiev/UA

Abstract

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Introduction: Lack of effectiveness of most immunotherapy methods requires new approaches. One of the most promising approaches, intensively investigated worldwide, is combined therapy based on dendritic cells (DC) and low-dose chemotherapy. The using of low-dose chemotherapy reduces the tumor's suppressor component, which in turn decreases the suppression of the immune system of cancer patients. The aim: to investigate the effect of chemo-immunotherapy on the suppression component of the immune system in murine sarcoma-37 (S37) model.

Methods: In experimental investigation 80 CBA mice have been involved. S37 was injected intramuscular at lethal dose (2*106 cells per animal). Cisplatin was administered intraperitoneally five times according to the two schemes: 0.2 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 4 day after the chemotherapy with 3 days interval.

Results: We have found that both of the proposed chemoimmunotherapy schemes had a significant antitumor and immunomodulation effect. The most pronounced effect was observed when used DC-vaccine and cisplatin at dose of 2 mg/kg in combination. Combination of DC vaccine and 2 mg/kg cisplatin had a synergistic effect: significantly decreasing of primary tumor volume in animals compared to the control (p = 0.001) and DC-vaccine (p = 0.007) groups have been found. We have shown that administration of DC vaccine and 2 mg/kg cispatin decreases the TGF- mRNA expression level in the tumor microenvironment (Υ = 0.0013) compared with the control group. Moreover, the administration of this combined therapy decrease VEGF mRNA expression level in tumor microenvironment in 2 times (Υ = 0.005) compared with the control group.

Conclusions: Low-dose cisplatin in combination with DC-vaccine reduces immunosuppression and neoangiogenesis in the tumor microenvironment.