Active immunization using dendritic cells mixed with tumor cells inhibits the growth of primary breast cancer.

Abstract

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). DCs were grown from Balb/c mice by culturing lymphocyte-immunodepleted bone marrow in murine granulocyte-macrophage colony-stimulating 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 groups were given intradermal inoculations of phosphate-buffered saline solution, 1 x 10(6) DCs, or lethally irradiated 4T1 cells alone. Booster intraperitoneal immunizations of 2 x 10(6) lethally irradiated 4T1 cells 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. Animals were examined daily, and tumor volume was recorded twice weekly with calipers. At 21 days there was a significant reduction in tumor growth in mice immunized with DCs mixed with irradiated 4T1 cells as compared with the control groups (p = 0.0005, Kruskal-Wallis test). These results suggest that DCs mixed with tumor cells as a source of undefined tumor antigen can induce an effective antitumor immune response. This finding provides a rationale for the use of cultured DCs in immunotherapy of breast and other cancers.