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Immune Complex-Loaded Dendritic Cells Are Superior to Soluble Immune Complexes as Antitumor Vaccine¹

Danita H. Schuurhuis^2,*, Nadine van Montfoort^3,*, Andreea Ioan-Facsinay^3,4,, Reshma Jiawan^*, Marcel Camps^*, Jan Nouta^*, Cornelis J. M. Melief^*, J. Sjef Verbeek and Ferry Ossendorp^5,*

^* Department of Immunohematology and Blood Transfusion and Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

Dendritic cells (DCs) play an important role in the induction of T cell responses. FcRs, expressed on DCs, facilitate the uptake of complexed Ag, resulting in efficient MHC class I and MHC class II Ag presentation and DC maturation. In the present study, we show that prophylactic immunization with DCs loaded with Ag-IgG immune complexes (ICs) leads to efficient induction of tumor protection in mice. Therapeutic vaccinations strongly delay tumor growth or even prevent tumors from growing out. By depleting CD4⁺ and CD8⁺ cell populations before tumor challenge, we identify CD8⁺ cells as the main effector cells involved in tumor eradication. Importantly, we show that DCs that are preloaded in vitro with ICs are at least 1000-fold more potent than ICs injected directly into mice or DCs loaded with the same amount of noncomplexed protein. The contribution of individual FcRs to Ag presentation, T cell response induction, and induction of tumor protection was assessed. We show that FcRI and FcRIII are capable of enhancing MHC class I-restricted Ag presentation to CD8⁺ T cells in vitro and that these activating FcRs on DCs are required for efficient priming of Ag-specific CD8⁺ cells in vivo and induction of tumor protection. These findings show that targeting ICs via the activating FcRs to DCs in vitro is superior to direct IC vaccination to induce protective tumor immunity in vivo.

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