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Infection-mimicking materials to program dendritic cells in situ

Abstract

Cancer vaccines typically depend on cumbersome and expensive manipulation of cells in the laboratory, and subsequent cell transplantation leads to poor lymph-node homing and limited efficacy. We propose that materials mimicking key aspects of bacterial infection may instead be used to directly control immune-cell trafficking and activation in the body. It is demonstrated that polymers can be designed to first release a cytokine to recruit and house host dendritic cells, and subsequently present cancer antigens and danger signals to activate the resident dendritic cells and markedly enhance their homing to lymph nodes. Specific and protective anti-tumour immunity was generated with these materials, as 90% survival was achieved in animals that otherwise die from cancer within 25 days. These materials show promise as cancer vaccines, and more broadly suggest that polymers may be designed to program and control the trafficking of a variety of cell types in the body.

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Figure 1: The concentration-dependent effects of GM-CSF on dendritic-cell proliferation, recruitment, activation and emigration in vitro and implications for in situ programming systems.
Figure 2: In vivo control of dendritic-cell recruitment and programming.
Figure 3: Batches of dendritic cells programmed in situ infer anti-tumour immunity.
Figure 4: Infection-mimicking microenvironment confers potent anti-tumour immunity.
Figure 5: Infection mimics amplify T-helper type-1 induction and promote antigen specification during immune responses.

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Acknowledgements

We are grateful to the Bauer research centres at Harvard University for assistance in NanoDrop measurements of nucleotide content. We thank B. Tilton for technical assistance with flow cytometry. The project has been made possible by NIH financial support (NIH R01 DE013033) and internal financial support at Harvard University to D.J.M.

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The experiments were designed by O.A., D.J.M. and G.D. and carried out by O.A., N.H. and L.C. The manuscript was written by O.A. and D.J.M. The principal investigator is D.J.M.

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Correspondence to David J. Mooney.

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Ali, O., Huebsch, N., Cao, L. et al. Infection-mimicking materials to program dendritic cells in situ. Nature Mater 8, 151–158 (2009). https://doi.org/10.1038/nmat2357

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