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

Surgery. 1997 Aug;122(2):228-34. doi: 10.1016/s0039-6060(97)90013-1.

Abstract

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.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow Cells*
  • Cell Culture Techniques / methods
  • Cell Differentiation
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Immunotherapy, Active*
  • Lymphocyte Depletion
  • Male
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology*
  • Mammary Neoplasms, Experimental / therapy
  • Mice
  • Mice, Inbred BALB C
  • Phenotype
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor