Improved immunostimulatory function of bone marrow derived macrophages transduced with the granulocyte-macrophage colony stimulating factor gene

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Abstract

Professional antigen presenting cells (APCs) play a prominent role in generation of antitumor immunity. Granulocyte macrophage colony stimulator factor (GM-CSF) has been shown to increase antigen presenting capacity of macrophages and dendritic cells. We examined whether retroviral mediated gene transfer of the murine GM-CSF cDNA into bone marrow precursor cells would result in generation of mature APCs with improved immunostimulatory function. We show that murine bone marrow cells can be stably transduced to produce GM- CSF (200-300 pg/mL per 106 cells in 24 hours). These cells proliferated in the absence of exogenous growth factor for 25 days and expressed the macrophage markers Mac-1, Mac-3 and F4/80, GM-CSF transduced bone marrow cells had enhanced stimulatory capacity in a primary mixed lymphocyte-APC reaction and improved antigen presenting function in a T helper clone proliferation assay. These data demonstrate that bone marrow cells can be genetically engineered to secrete GM-CSF resulting in expansion of effective APCs. GM-CSF transduced APCs may be used as natural adjuvants in stimulating immune responses in vivo.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalCancer Biotherapy and Radiopharmaceuticals
Volume12
Issue number1
StatePublished - Feb 1997
Externally publishedYes

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Granulocyte-Macrophage Colony-Stimulating Factor
Antigen-Presenting Cells
Macrophages
Granulocytes
Bone Marrow Cells
Genes
Antigens
Dendritic Cells
Immunity
Intercellular Signaling Peptides and Proteins
Complementary DNA
Clone Cells
Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

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title = "Improved immunostimulatory function of bone marrow derived macrophages transduced with the granulocyte-macrophage colony stimulating factor gene",
abstract = "Professional antigen presenting cells (APCs) play a prominent role in generation of antitumor immunity. Granulocyte macrophage colony stimulator factor (GM-CSF) has been shown to increase antigen presenting capacity of macrophages and dendritic cells. We examined whether retroviral mediated gene transfer of the murine GM-CSF cDNA into bone marrow precursor cells would result in generation of mature APCs with improved immunostimulatory function. We show that murine bone marrow cells can be stably transduced to produce GM- CSF (200-300 pg/mL per 106 cells in 24 hours). These cells proliferated in the absence of exogenous growth factor for 25 days and expressed the macrophage markers Mac-1, Mac-3 and F4/80, GM-CSF transduced bone marrow cells had enhanced stimulatory capacity in a primary mixed lymphocyte-APC reaction and improved antigen presenting function in a T helper clone proliferation assay. These data demonstrate that bone marrow cells can be genetically engineered to secrete GM-CSF resulting in expansion of effective APCs. GM-CSF transduced APCs may be used as natural adjuvants in stimulating immune responses in vivo.",
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N2 - Professional antigen presenting cells (APCs) play a prominent role in generation of antitumor immunity. Granulocyte macrophage colony stimulator factor (GM-CSF) has been shown to increase antigen presenting capacity of macrophages and dendritic cells. We examined whether retroviral mediated gene transfer of the murine GM-CSF cDNA into bone marrow precursor cells would result in generation of mature APCs with improved immunostimulatory function. We show that murine bone marrow cells can be stably transduced to produce GM- CSF (200-300 pg/mL per 106 cells in 24 hours). These cells proliferated in the absence of exogenous growth factor for 25 days and expressed the macrophage markers Mac-1, Mac-3 and F4/80, GM-CSF transduced bone marrow cells had enhanced stimulatory capacity in a primary mixed lymphocyte-APC reaction and improved antigen presenting function in a T helper clone proliferation assay. These data demonstrate that bone marrow cells can be genetically engineered to secrete GM-CSF resulting in expansion of effective APCs. GM-CSF transduced APCs may be used as natural adjuvants in stimulating immune responses in vivo.

AB - Professional antigen presenting cells (APCs) play a prominent role in generation of antitumor immunity. Granulocyte macrophage colony stimulator factor (GM-CSF) has been shown to increase antigen presenting capacity of macrophages and dendritic cells. We examined whether retroviral mediated gene transfer of the murine GM-CSF cDNA into bone marrow precursor cells would result in generation of mature APCs with improved immunostimulatory function. We show that murine bone marrow cells can be stably transduced to produce GM- CSF (200-300 pg/mL per 106 cells in 24 hours). These cells proliferated in the absence of exogenous growth factor for 25 days and expressed the macrophage markers Mac-1, Mac-3 and F4/80, GM-CSF transduced bone marrow cells had enhanced stimulatory capacity in a primary mixed lymphocyte-APC reaction and improved antigen presenting function in a T helper clone proliferation assay. These data demonstrate that bone marrow cells can be genetically engineered to secrete GM-CSF resulting in expansion of effective APCs. GM-CSF transduced APCs may be used as natural adjuvants in stimulating immune responses in vivo.

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