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Gene Ther. 2000 Apr;7(8):707-13.

Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factor and interferon-gamma.

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1
Department of Immunology, Second Military Medical University, Shanghai, PR China.

Abstract

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.

PMID:
10800095
DOI:
10.1038/sj.gt.3301162
[Indexed for MEDLINE]
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