Modern chemoimmunotherapy approach based on dendritic cells and low-dose cisplatin in experiment

Gorbach A., Khranovska N.M., Skachkova O., Sydor R.I., Svergun N.M.

A. Gorbach, N. Khranovska, O. Skachkova, R. Sydor, N. Svergun

National Cancer Institute, Kyiv, Ukraine

horbach.alex@gmail.com

Introduction: Nowadays, combined therapy based on dendritic cells (DC) and low-dose chemotherapy is intensively investigated worldwide. There are no commonly accepted regimens of combined therapy and development of efficient chemoimmunotherapy schemes remains an actual problem. Aim: To develop scheme of combined chemoimmunotherapy based on DC and low-dose cisplatin. Materials and Methods: 120 CBA mice have been involved in the experiment. Sarcoma-37 was injected intramuscularly at lethal dose (2×106 cells per animal). Cisplatin was injected intraperitoneally 5 times in metronomic regimen 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 the 4 day after the chemotherapy. All experiments were approved by Ethical Committee permission of National Cancer Institute (Kyiv, Ukraine). Results: We have found that both chemoimmunotherapy schemes had significant antitumor and immunomodulation effect. The most pronounced effect was observed with DC-vaccine and cisplatin at concentration of 2 mg/kg in combination. Combination of DC vaccine and low-dose cisplatin had a synergistic effect on the reduction of primary tumor. Significantly decrease of primary tumor volume in animals was received in combined therapy compared to the control (= 0.001) and DC-vaccine (= 0.007) groups have been found. We showed that administration of combined therapy improves survival by 20% in comparison with the control group. A significant increase of cytotoxic activity of splenocytes in response to allogeneic stimulation to 42.33 ± 4.8% in the combined therapy group compared to 29.67 ± 4.1% in the control group had been observed, < 0.05. We also found that phagocytic activity of splenocytes in this group increased up to 52.33 ± 4.67% compared to 37 ± 5.29% in the control group, p < 0.05. The coefficient of reactive oxygen species induction was statistically significant and increased to 1.61 ± 0.23 in comparison with 1.05 ± 0.13 in the control group. Conclusions: Low-dose chemotherapeutics enhance the antitumor effect of DC-based immunotherapy. These investigations form the basis to a new multimodality treatment of cancer patients.

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