ACTIVE IMMUNIZATION USING DENDRITIC CELLS MIXED WITH TUMOR-CELLS INHIBITS THE GROWTH OF PRIMARY BREAST-CANCER

Background. Dendritic cells (DCs) are potent antigen-presenting cells regarded as crucial in the priming of an immune response. The goal of our study was to test whether bone marrow-generated DCs are capable of inducing protective immunity against a murine breast carcinoma (4T1). Methods. DCs were grown from Balb/c mice by culturing lymphocyte-immu nodepleted bone marrow in murine granulocyte-macrophage colony-stimula ting factor containing medium for 10 days. Balb/c mice (five to eight per group) were immunized intradermally with 1 x 10(6) DCs mixed with 2 x 10(6) lethally irradiated 4T1 cells on day 0. Mice in control grou ps were given intradermal inoculations of phosphate-buffered saline so lution, 1 x 10(6) DCs, or lethally irradiated 4T1 cells alone. Booster intraperitoneal immunizations of 2 x 10(6) lethally irradiated 4T1 ce lls were given on days 7 and 14. All mice were challenged with 5 x 10( 3) 4T1 cells subcutaneously 7 days after the final immunization. Anima ls were examined daily, and tumor volume was recorded twice weekly wit h calipers.Results. At 21 days there was a significant reduction in tu mor growth in mice immunized with DCs mixed with irradiated 4T1 cells as compared with control groups (p = 0.0005, Kruskal-Wallis test). Con clusions. These results suggest that DCs mixed with tumor cells as a s ource of undefined tumor antigen can induce an effective antitumor imm une response. This finding provides a rationale for the use of culture d DCs in immunotherapy of breast and other cancers.