Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factor and interferon-gamma.
Adoptive transfer of activated macrophages, being both effector cells and antigen-presenting cells, represents a promising approach to immunotherapy of cancer. In order to get activated macrophages with increased antitumor potential, in the present study, murine peritoneal macrophages were transduced with human macrophage colony-stimulating factor (M-CSF) and murine interferon-gamma (IFNgamma) by recombinant adenovirus infection. The results demonstrate that M-CSF and IFNgamma gene-modified macrophages exhibited higher expression of MHC-II, B7.1 and ICAM-1, increased antigen-presenting activity and cytotoxicity. It was also shown that they secreted more tumor necrosis factor, interleukin-1 and nitric oxide. In vivo experiments showed that in previously initiated murine pulmonary metastatic melanoma, tumor lysate-pulsed, M-CSF and IFNgamma gene-modified macrophages elicited more potent antitumor effects than tumor lysate pulsed M-CSF or IFNgamma gene-modified macrophages. Cytotoxic T lymphocyte (CTL) activity, IFNgamma and tumor-necrosis factor production of the splenocytes increased significantly in mice after intravenous injection of the gene-modified macrophages. M-CSF and IFNgamma gene-modified macrophages may act as activated effector and antigen-presenting cells, thus eliciting a more potent antitumor response.
Lei
H
H
Department of Immunology, Second Military Medical University, Shanghai, PR China.
Ju
D W
DW
Yu
Y
Y
Tao
Q
Q
Chen
G
G
Gu
S
S
Hamada
H
H
Cao
X
X
D000818:Animals; D017951:Antigen Presentation; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma