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-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.


RESULTS
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).


CONCLUSIONS
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.
Coveney
E
E
Department of Surgery, Duke University Medical Center, Durham, N.C. 27710, USA.
Wheatley
G H
GH
Lyerly
H K
HK
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016233:Immunotherapy, Active; D008212:Lymphocyte Depletion; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016178:Granulocyte-Macrophage Colony-Stimulating Factor