Despite many improvement efforts, effects of chemotherapy are still unsatisfactory. The combination treatment with the use of cytostatics followed by immunotherapy may augment their antitumor effect. Therapeutic efficiency of two cytostatics cyclophosphamide (CY) and 5-fluorouracil (5-FU) combined with cellular vaccines were compared in mice bearing s.c. growing MC38 colon carcinoma. Vaccines have consisted of bone morrow derived dendritic cells stimulated with tumor lysate (BM-DC/TAg) and IL-2-transduced MC38(MC38/IL-2) cells which produced aproximally 100 LU cytokine/ml/5x10⁶cells/48h. Cytostatics (150 mg/kg body weight) were administered i.p. on the 14th day after tumor inoculation. Applications of cellular vaccines were given in two consecutive weeks, starting 3 days after drug administration. Administration of CY caused statistically significant higher tumor growth delay compared with 5-FU. Combination of CY with BM-DC/TAg and/or MC38/IL-2 moderately enhanced the effect of the cytostatic activity and percentage of CD8⁺ cells accompanied by augmented IFN-gamma production by restimulated in vitro splenocytes. No considerable changes in percentage of CD49b⁺ cells after application of CY and cellular vaccines were observed. On the other hand, the administration of 5FU caused slight increase in percentage of CD4⁺ among restimulated splenocytes. Besides, 5FU +/- cellular vaccines influenced on augmentation of Treg cell (CD4⁺CD25⁺Foxp3⁺) number in freshly isolated splenocyte population. Our findings suggest that repeated peritumoral application of BM-DC/TAg together with IL-2-producing tumor cells can inhibit tumor growth also by engage of cell influx into tumor tissue. Although cellular vaccine moderately affect tumor growth reduction, they can act as activators able to accelerate effect of anti-tumor response and could be useful as an adjuvant vaccine in combined chemo-immunotherapy of experimental murine tumors.

This work was supported by grant of the Polish Ministry of Science and Higher Education No N N401 235334.

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1. COMBINATION OF: IMATINIB, PRI-2191 AND CYTOSTATICS - THE ANTIPROLIFERATIVE EFFECTS ON HL-60 LEUKEMIA CELL LINE