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Combined CXC chemokine and interleukin-12 gene transfer enhances antitumor immunity

Gene Therapy volume 8, pages 282–290 (2001)Cite this article

Abstract

It has been shown that intratumor administration of an adenovirus vector expressing IL-12 produces a potent T cell-mediated response that leads to significant tumor regression in a murine breast cancer model. IP-10 and MIG are CXC chemokines that recruit mononuclear cells in vivo. In addition to their chemotactic roles, IP-10 and MIG inhibit angiogenesis. We tested whether the addition of IP-10 or MIG may both enhance the antitumor immune response of IL-12 through T cell recruitment and inhibit tumor growth through angiostasis. Adenovirus vectors expressing IP-10 or MIG and/or IL-12 were administered intratumorally in a murine model of mammary adenocarcinoma and fibrosarcoma. Administration of IP-10 or MIG in combination with IL-12 resulted in considerable tumor regression and increased survival time of tumor-bearing animals as compared with IP-10, MIG, IL-12 alone or control-treated animals, with the IP-10 IL-12 combination being most effective. These results suggest augmenting the antitumor immune response and inhibiting tumor angiogenesis with adenoviral vectors expressing IP-10 in combination with IL-12 is a novel way to enhance tumor regression.

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Acknowledgements

We acknowledge the excellent technical help of Duncan Chong and Xueya Feng. This work is funded by the Medical Research Council (Canada).

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  1. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada

    K Palmer, M Hitt, PCR Emtage, S Gyorffy & J Gauldie

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  1. K Palmer
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  4. S Gyorffy
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Palmer, K., Hitt, M., Emtage, P. et al. Combined CXC chemokine and interleukin-12 gene transfer enhances antitumor immunity. Gene Ther 8, 282–290 (2001). https://doi.org/10.1038/sj.gt.3301386

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