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Monocyte chemoattractant protein-1 (MCP-1) gene transduction: an effective tumor vaccine strategy for non-intracranial tumors

  • Original Article
  • Tumour Vaccine, MCP-1, Malignant Glioma, 9L Gliosarcoma Model
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Recently, there has been renewed interest in the concept of tumor vaccines using genetically engineered tumor cells expressing a variety of cytokines to increase their immunogenicity. Human MCP-1 (JE) is a potent chemoattractant and activator of monocytes and T lymphocytes and thus a good candidate gene for a tumor vaccine. We therefore evaluated the efficacy of vaccines consisting of irradiated tumor cells transduced with the murine MCP-1 gene in the syngeneic 9L gliosarcoma brain tumor model. 9L cell lines stably expressing murine MCP-1 (9L-JE) and control cell lines expressing neomycin 3′ phosphotransferase (9L-Neo) were generated by infection with a Moloney murine leukemia retroviral vector. Fisher 344 rats were immunized with intradermal injections of 5×105 or 2×106 irradiated (5000 cGy) 9L-JE, 9L-Neo, and wild-type 9L (9L-WT) cells. Two weeks later immunized an non-immunized animals were challenged with varyious doses of intradermal (5×106–5×107) or intracerebral (2×104–5×105) 9L-WT cells. Intradermal tumors grew in all non-immunized animals. No tumors grew in animals immunized with irradiated 9L-JE or 9L-Neo cells and challenged with inocula of fewer than 5×105 9L-WT cells. With higher inocula up to 107 cells, tumors appeared in all the animals. Tumors in animals immunized with 9L-JE were always smaller than tumors in the other groups. In addition, only the 9L-JE vaccine protected against tumor inocula of 5×107 cells. Thus vaccination with MCP-1-expressing cells was able to protect animals against at least a 100-fold larger number of challenge tumor cells than vaccination with control cells. In contrast to studies with intradermal tumors, immunization with 9L-JE and 9L-Neo produced only minimal protection against intracerebral tumors. There was no significant difference between the 9L-JE and 9L-Neo vaccines in intracerebral challenge. This study suggests that tumor vaccines expressing cytokine genes such as MCP-1 can increase the antitumor response. However, the protective effect of these vaccines appears to be largely limited to intradermal tumors rather than intracerebral tumors.

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Authors and Affiliations

  1. Division of Cancer Pharmacology, Room 1740, Dana-Farber Cancer Institute, 44 Binney St., 02115, Boston, MA, USA

    Yoshinobu Manome, Ari Hershowitz, Toshihide Tanaka, Donald W. Kufe & Howard A. Fine

  2. Division of Neurology, Brigham and Women's Hospital, Harvard Medical School, 02115, Boston, MA, USA

    Patrick Y. Wen

  3. Division of Medical Oncology, Dana Farber Cancer Institute, 32115, Boston, MA, USA

    Barrett J. Rollins

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  1. Yoshinobu Manome
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Manome, Y., Wen, P.Y., Hershowitz, A. et al. Monocyte chemoattractant protein-1 (MCP-1) gene transduction: an effective tumor vaccine strategy for non-intracranial tumors. Cancer Immunol Immunother 41, 227–235 (1995). https://doi.org/10.1007/BF01516997

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  • DOI: https://doi.org/10.1007/BF01516997

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