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Induction of anti-tumor immunity by vaccination with dendritic cells pulsed with anti-CD44 IgG opsonized tumor cells

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Abstract

Due to the pivotal role that dendritic cells (DC) play in eliciting and maintaining functional anti-tumor T cell responses, these APC have been exploited against tumors. DC express several receptors for the Fc portion of IgG (Fcγ receptors) that mediate the internalization of antigen-IgG complexes and promote efficient MHC class I and II restricted antigen presentation. In this study, the efficacy of vaccination with DC pulsed with apoptotic B16 melanoma cells opsonized with an anti-CD44 IgG (B16-CD44) was explored. Immature bone marrow derived DC grown in vitro with IL-4 and GM-CSF were pulsed with B16-CD44. After 48 h of pulsing, maturation of DC was demonstrated by production of IL-12 and upregulation of CD80 and CD40 expression. To test the efficacy of vaccination with DC+B16-CD44, mice were vaccinated subcutaneously Lymphocytes from mice vaccinated with DC+B16-CD44 produced IFN-γ in response to B16 melanoma lysates as well as an MHC class I restricted B16 melanoma-associated peptide, indicating B16 specific CD8 T cell activation. Upon challenge with viable B16 cells, all mice vaccinated with DC alone developed tumor compared to 40% of mice vaccinated with DC+B16-CD44; 60% of the latter mice remained tumor free for at least 8 months. In addition, established lung tumors and distant metastases were significantly reduced in mice treated with DC+B16-CD44. Lastly, delayed growth of established subcutaneous tumors was induced by combination therapy with anti-CD44 antibodies followed by DC injection. This study demonstrates the efficacy of targeting tumor antigens to DC via Fcγ receptors.

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Acknowledgments

This work has been supported in part by the Flow Cytometry Core and the Analytic Microscopy Core Facilities at the H. Lee Moffitt Cancer Center and Research Institute. Supported by grants from the National Cancer Institute/National Institute of Health (1 R01 CA71669, 1R01 CA87019, 5 PO1 CA59327).

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Authors and Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., SRB-3 Room 23244, Tampa, FL, 33612, USA

    Shari Pilon-Thomas, Lisa Kuhn, Adam Riker & James J Mulé

  2. University of Michigan Medical Center, Ann Arbor, MI, USA

    Monique Verhaegen

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  1. Shari Pilon-Thomas
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  2. Monique Verhaegen
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Correspondence to Shari Pilon-Thomas.

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Pilon-Thomas, S., Verhaegen, M., Kuhn, L. et al. Induction of anti-tumor immunity by vaccination with dendritic cells pulsed with anti-CD44 IgG opsonized tumor cells. Cancer Immunol Immunother 55, 1238–1246 (2006). https://doi.org/10.1007/s00262-005-0104-8

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