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Taking lessons from dendritic cells: multiple xenogeneic ligands for leukocyte integrins have the potential to stimulate anti-tumor immunity

Gene Therapy volume 6, pages 1835–1844 (1999)Cite this article

Abstract

Expression of large numbers of different costimulatory integrin ligands (CILs) attributes dendritic cells with an ability to induce primary anti-tumor immune responses. Here, we show that optimized gene transfer of the xenogeneic (human) CILs VCAM-1, MAdCAM-1 and ICAM-1 causes rapid and complete rejection of established mouse EL-4 tumors, and generates prolonged systemic anti-tumor immunity; whereas human E-cadherin weakly slows tumor growth. In each case the immune response was mediated by CD8+ T cells and NK cells, accompanied by augmented tumor-specific cytolytic T cell (CTL) activity involving both the perforin and Fas-ligand pathways. Adoptive transfer of splenocytes from cured mice rapidly cleared established tumors in recipients. The mechanism for CIL-mediated immunity is unknown, but may involve CTL-facilitated tumor lysis, since CTLs were generally twice as efficient at killing CIL-transfected tumor cells than parental tumor cells. Optimized CIL-based gene therapy may provide an approach to complement or replace conventional DC adoptive cell therapy for suppressing tumor growth.

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Acknowledgements

This work was supported in part by grants from the Royal Society of New Zealand, the Cancer Society of New Zealand, The Lottery Grants Board, The Leukaemia and Blood Foundation, the Health Research Council of New Zealand, and the Maurice and Phyllis Paykel Trust. GWK is a James Cook Research Fellow funded by the Royal Society of New Zealand.

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

    J R Kanwar, R W Berg, K Lehnert & G W Krissansen

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  4. G W Krissansen
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Kanwar, J., Berg, R., Lehnert, K. et al. Taking lessons from dendritic cells: multiple xenogeneic ligands for leukocyte integrins have the potential to stimulate anti-tumor immunity. Gene Ther 6, 1835–1844 (1999). https://doi.org/10.1038/sj.gt.3301016

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