Established B16 tumors are rejected following treatment with GM-CSF-secreting tumor cell immunotherapy in combination with anti-4-1BB mAb

Clin Immunol. 2007 Oct;125(1):76-87. doi: 10.1016/j.clim.2007.07.005. Epub 2007 Aug 13.


Immunization with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific and long lasting anti-tumor immunity in clinical and preclinical settings. Efforts to further increase immunotherapy efficacy with immune-modulatory agents are under evaluation. Based on the immune-modulatory properties of 4-1BB (CD137), it has been postulated that agonistic 4-1BB antibodies may add additional anti-tumor efficacy to GM-CSF-secreting tumor cell immunotherapy. The combination of GM-CSF-secreting tumor cell immunotherapy and anti-4-1BB monoclonal antibody (mAb) treatment resulted in rejection of established tumors in the B16 melanoma model. These anti-tumor effects correlated with persistent tumor-specific CD8(+) T cell responses. In addition, early tumor infiltration of functional CD8(+) T cells and a greater expansion of antigen-specific memory T cells were found in mice treated with the combination therapy. In summary, an agonistic anti-4-1BB mAb combined with GM-CSF-secreting tumor cell immunotherapy may provide a novel and potent treatment strategy for patients with cancer.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Female
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Immunologic Factors / immunology
  • Immunologic Factors / therapeutic use*
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation / immunology
  • Lymphocyte Subsets / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Tumor Necrosis Factor Receptor Superfamily, Member 9* / immunology


  • Antibodies, Monoclonal
  • Immunologic Factors
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Granulocyte-Macrophage Colony-Stimulating Factor