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  • Cell-Based Therapy
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Cell-Based Therapy

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

Gene Therapy volume 7, pages 707–713 (2000)Cite this article

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-γ (IFNγ) by recombinant adenovirus infection. The results demonstrate that M-CSF and IFNγ 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 IFNγ gene-modified macrophages elicited more potent antitumor effects than tumor lysate pulsed M-CSF or IFNγ gene-modified macrophages. Cytotoxic T lymphocyte (CTL) activity, IFNγ and tumor-necrosis factor production of the splenocytes increased significantly in mice after intravenous injection of the gene-modified macrophages. M-CSF and IFNγ gene-modified macrophages may act as activated effector and antigen-presenting cells, thus eliciting a more potent antitumor response.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (39825123, 39780025).

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Authors and Affiliations

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

    H Lei, D W Ju, Y Yu, Q Tao, G Chen, S Gu & X Cao

  2. Department of Molecular Biotherapy Research, Japanese Foundation of Cancer Research, Tokyo, Japan

    H Hamada

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Lei, H., Ju, D., Yu, Y. et al. Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factor and interferon-γ. Gene Ther 7, 707–713 (2000). https://doi.org/10.1038/sj.gt.3301162

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