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Inhibition and promotion of tumor growth with adeno-associated virus carcinoembryonic antigen vaccine and Toll-like receptor agonists

Cancer Gene Therapy volume 18, pages 850–858 (2011)Cite this article

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Abstract

Carcinoembryonic antigen (CEA) is a cancer vaccines’ target. Several features of recombinant adeno-associated virus (rAAV) are attractive for vaccine applications. Combining other viral vector vaccines with Toll-like receptor (TLR) agonists enhances antitumor immunity. Wild-type and CEA transgenic (Tg) mice were immunized with rAAV-expressing CEA, the TLR9 agonist, oligodinucleotide (ODN)1826 and the TLR7 agonist, imiquimod. Mice were challenged with MC38 colon tumor cells and MC38 cells expressing CEA. rAAV-CEA immunization combined with ODN1826 or imiquimod enhanced CEA-specific T-helper 1 immunity and protected against tumor challenge in wild-type but not in CEA-Tg mice. In contrast, immunization with rAAV-CEA in CEA-Tg mice could abrogate the antitumor effects of ODN1826 and promote tumor growth. Compared to wild-type, CEA-Tg mice were characterized by a greater myeloid suppressor cell and T-helper 2 response to TLR agonists and to syngeneic tumors. Depleting PDCA1+ plasmacytoid dendritic cells and Gr1+ myeloid cells increased anti-CEA immune responses in CEA-Tg mice to rAAV-CEA-ODN1826 immunization, whereas depleting CD25+ T cells did not. There are differences in the response of wild-type and CEA-Tg mice to rAAV-CEA, TLR agonists and syngeneic tumor. In CEA-Tg mice, tumor growth can be promoted with rAAV-CEA and TLR agonists. Dendritic and myeloid cells play a regulatory role.

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Acknowledgements

This work was supported by National Institutes of Health Grants R01CA118660 and R01CA132077.

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Authors and Affiliations

  1. Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    P L Triozzi & W Aldrich

  2. Department of Pathology and the Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA

    S Ponnazhagan

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Correspondence to P L Triozzi.

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Triozzi, P., Aldrich, W. & Ponnazhagan, S. Inhibition and promotion of tumor growth with adeno-associated virus carcinoembryonic antigen vaccine and Toll-like receptor agonists. Cancer Gene Ther 18, 850–858 (2011). https://doi.org/10.1038/cgt.2011.54

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