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Antitumor activity of dual-specific T cells and influenza virus

Cancer Gene Therapy volume 14, pages 499–508 (2007)Cite this article

Abstract

Activation and expansion of T cells are important in disease resolution, but tumors do not usually satisfy these immune requirements. Therefore, we employed a novel strategy whereby dual-specific T cells were generated that could respond to both tumor and influenza virus, reasoning that immunization with influenza virus would activate and expand tumor-specific cells, and inhibit tumor growth. Dual-specific T cells were generated by gene modification of influenza virus-specific mouse T cells with a chimeric gene-encoding reactivity against the erbB2 tumor-associated antigen. Dual-specific T cells were demonstrated to respond against both tumor and influenza in vitro, and expanded in vitro in response to influenza to a much greater degree than in response to tumor cells. Following adoptive transfer and immunization of tumor-bearing mice with influenza virus, dual-specific T cells expanded greatly in numbers in the peritoneal cavity and spleen. This resulted in a significant increase in time of survival of mice. However, tumors were not eradicated, which may have been due to the observed poor penetration of tumor by T cells. This is the first demonstration that the potent immunogenic nature of an infectious agent can be utilized to directly impact on T-cell expansion and activity against tumor in vivo.

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Acknowledgements

This work was supported by grants from The National Health and Medical Research Council of Australia (NHMRC), The Cancer Council of Australia, The Bob Parker Memorial Trust and the Peter MacCallum Cancer Centre Foundation. MK is supported by a Career Development Award from the National Breast Cancer Foundation and NHMRC.

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Authors and Affiliations

  1. Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Australia

    A Murphy, J A Westwood, M W L Teng, M Moeller, Y Xu, M J Smyth, P K Darcy & M H Kershaw

  2. Department of Microbiology and Immunology, University of Melbourne, Australia

    L E Brown & M J Smyth

  3. Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    P Hwu

  4. Department of Pathology, University of Melbourne, Australia

    P K Darcy & M H Kershaw

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  1. A Murphy
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  2. J A Westwood
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Correspondence to M H Kershaw.

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Murphy, A., Westwood, J., Brown, L. et al. Antitumor activity of dual-specific T cells and influenza virus. Cancer Gene Ther 14, 499–508 (2007). https://doi.org/10.1038/sj.cgt.7701034

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