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Mouse B7-H3 induces antitumor immunity

Gene Therapy volume 10, pages 1728–1734 (2003)Cite this article

Abstract

Members of the B7 family costimulate the proliferation of lymphocytes during the initiation and maintenance of antigen-specific humoral and cell-mediated immune responses. While B7-1 and -2 are restricted to lymphoid tissues, and activate naïve T cells, recently identified members including B7-H2 and -H3 are widely expressed on nonlymphoid tissues, and regulate effector lymphocytes in the periphery. B7-H3 has properties that suggested it may display antitumor activity, including the ability to stimulate Th1 and cytotoxic T-cell responses. Here, we test this notion by determining whether intratumoral injection of an expression plasmid encoding a newly described mouse homologue of B7-H3 is able to eradicate EL-4 lymphomas. Intratumoral injection of a mouse B7-H3 pcDNA3 expression plasmid led to complete regression of 50% tumors, or otherwise significantly slowed tumor growth. Mice whose tumors completely regressed resisted a challenge with parental tumor cells, indicating systemic immunity had been generated. B7-H3-mediated antitumor immunity was mediated by CD8+ T and NK cells, with no apparent contribution from CD4+ T cells. In summary, the results indicate that B7-H3 interactions may play a role in regulating cell-mediated immune responses against cancer, and that B7-H3 is a potential therapeutic tool.

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Acknowledgements

This work was supported in part by grants from The Wellcome Trust, the Royal Society of New Zealand, the Health Research Council of New Zealand, and the Maurice and Phyllis Paykel Trust. XS and MV contributed equally to the work. XS is a recipient of a Wellcome Trust Research Leave Fellowship. MV was a recipient of an HRC Junior Award in Health Research.

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Authors and Affiliations

  1. Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand

    X Sun, M Vale, E Leung, J R Kanwar, R Gupta & G W Krissansen

  2. Department of Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, People's Republic of China

    X Sun

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  1. X Sun
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  2. M Vale
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Sun, X., Vale, M., Leung, E. et al. Mouse B7-H3 induces antitumor immunity. Gene Ther 10, 1728–1734 (2003). https://doi.org/10.1038/sj.gt.3302070

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