Low-dose conventional chemotherapeutics synergizes with dendritic cell - based immunotherapy in antitumor activity
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1
Kyiv National Taras Shevchenko University, Educational and Scientific Centre «Institute of Biology», Ukraine
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2
National Cancer Institute of the Ministry of Public Health of Ukraine, Ukraine
Background. The benefit of combining low-dose chemotherapeutics with cancer vaccine therapy has not been established. Here we investigated the antitumor effect of conventional chemotherapeutics cyclophosphamide (CP) or doxorubicin (DOX), or cisplatin (CIS) in combination with DC-based immunotherapy in murine tumor models. Methods. Studies have been performed with 100 C57Bl/6 and 213 CBA mice with lethal dose of Lewis lung carcinoma (LLC) or sarcoma 37 (S37) respectively. DCs loaded with mechanoactivated lyophilized tumor cells have been used as immunotherapy agent. DCs were administered i/v three times with two-day interval. Low-dose chemotherapeutics were administered in “metronomic” regimen before DC-immunotherapy. Results. Addition of CP improved DC-immunotherapy leading to a significant decrease in the number and volume of metastases in lungs. Combination of DC-immunotherapy with DOX or CIS significantly improved median survival time of animals with S37 in comparison with control group. Metronomic chemotherapy resulted in a significant reduction in the proportions of T-reg cells and mRNA levels of immunosuppressive cytokines in the peripheral blood and lymph nodes lymphocytes. Addition of chemotherapeutics to DC-immunotherapy also augments Th-1 immune response, increases number of activated CD69+, CD54+, CD25+ splenocytes, enhance spleen macrophages phagocyte activity and reactive oxygen species (ROS) production, cytotoxic activity of NK-cells and CTL (p<0,05). Antitumor effectiveness of DC-immunotherapy combined with low-dose chemotherapeutics are associated with significant decrease in mRNA levels of TGF-β, VEGF, IL-10 in the residual tumor sites. Conclusions. Low-dose chemotherapeutics enhance the antitumor effect of DC-based immunotherapy. These findings form the basis to a new multimodality treatment in cancer patients.
Keywords:
Dendritic Cells,
Doxorubicin,
Cisplatin,
Cyclophosphamide,
Immunotherapy
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Gorbach
A,
Khranovska
N,
Pozur
V,
Skachkova
O,
Svergun
N,
Sydor
R and
Nikulina
V
(2013). Low-dose conventional chemotherapeutics synergizes with dendritic cell - based immunotherapy in antitumor activity.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00151
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Received:
11 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Alexander Gorbach, Kyiv National Taras Shevchenko University, Educational and Scientific Centre «Institute of Biology», Kyiv, 01601, Ukraine, horbach.alex@gmail.com