Recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy

Clin Immunol. 2007 May;123(2):155-65. doi: 10.1016/j.clim.2007.01.002. Epub 2007 Feb 22.

Abstract

IL-7 is known for its role in lymphopoiesis and T-cell homeostasis. In addition, its capacity to augment the immune response to weak or low affinity antigens makes it an ideal candidate to evaluate in combination with a GM-CSF-secreting tumor cell immunotherapy, which has been shown to elicit broad humoral and cellular immune responses. The studies reported here show that IL-7, when combined with a GM-CSF-secreting tumor cell immunotherapy, significantly prolonged the survival of tumor-bearing mice. The enhanced anti-tumor protection correlated with an increased number of activated dendritic cells (DC) and T cells in lymphoid tissues, such as the draining lymph nodes (DLN) and spleen. Moreover, an increased number of activated effector T cells were found in the tumor microenvironment, correlating with a more potent systemic tumor-specific T-cell response than each monotherapy alone. Taken together, these studies demonstrate that IL-7 augments the anti-tumor response of a GM-CSF-secreting tumor cell immunotherapy in preclinical models.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • CD11c Antigen / analysis
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Count
  • Cell Line, Tumor
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Interferon-gamma / analysis
  • Interleukin-7 / genetics
  • Interleukin-7 / pharmacology
  • Interleukin-7 / therapeutic use*
  • Lymphocyte Activation / drug effects
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lysosomal-Associated Membrane Protein 1 / analysis
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Membrane Glycoproteins / analysis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Survival Analysis
  • gp100 Melanoma Antigen

Substances

  • Adjuvants, Immunologic
  • CD11c Antigen
  • Cancer Vaccines
  • IL7 protein, human
  • Interleukin-7
  • Lysosomal-Associated Membrane Protein 1
  • Membrane Glycoproteins
  • PMEL protein, human
  • Pmel protein, mouse
  • Recombinant Proteins
  • gp100 Melanoma Antigen
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor