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Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response

Nature Nanotechnology volume 6, pages 645–650 (2011)Cite this article

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Abstract

Therapeutic cancer vaccination is an attractive strategy because it induces T cells of the immune system to recognize and kill tumour cells in cancer patients. However, it remains difficult to generate large numbers of T cells that can recognize the antigens on cancer cells using conventional vaccine carrier systems1,2. Here we show that α-Al2O3 nanoparticles can act as an antigen carrier to reduce the amount of antigen required to activate T cells in vitro and in vivo. We found that α-Al2O3 nanoparticles delivered antigens to autophagosomes in dendritic cells, which then presented the antigens to T cells through autophagy. Immunization of mice with α-Al2O3 nanoparticles that are conjugated to either a model tumour antigen or autophagosomes derived from tumour cells resulted in tumour regression. These results suggest that α-Al2O3 nanoparticles may be a promising adjuvant in the development of therapeutic cancer vaccines.

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Figure 1: Conjugation of OVA to α-Al2O3 nanoparticles resulted in efficient cross-presentation of the OVA antigen in vitro.
Figure 2: DCs pulsed with α-Al2O3–OVA efficiently cross-presented OVA antigen to naive OT-I T cells in vitro and in vivo.
Figure 3: Autophagy is required for α-Al2O3 nanoparticle-mediated cross-presentation of OVA to naive T cells.
Figure 4: α-Al2O3 nanoparticles increased the efficiency of cross-presentation and antitumour response of cancer vaccines.

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Acknowledgements

The authors thank W. J. Urba for critical reading of the manuscript and Y. Zhang, P. Pang and M. Eastman for help with the collection of experimental data. Thanks also go to N. Morris and A. D. Weinberg for providing the anti-OX40 antibody. This research is supported in part by the Safeway Foundation and Providence Portland Medical Foundation (H-M.H.), Oregon Nanoscience and Microtechnologies Institute (J.J. and H-M.H.), the National Science Foundation (J.J.) and the National Institutes of Health (R01CA107243 and R21CA141278 to H-M.H.).

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Authors and Affiliations

  1. Department of Physics, Portland State University, Portland, Oregon, USA

    Haiyan Li & Jun Jiao

  2. Laboratory of Cancer Immunobiology, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA

    Yuhuan Li & Hong-Ming Hu

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  1. Haiyan Li
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  2. Yuhuan Li
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Contributions

H.L. performed the experiments and wrote the manuscript. Y.L. performed some experiments. J.J. and H-M.H. directed this work and wrote the manuscript.

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Correspondence to Jun Jiao or Hong-Ming Hu.

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Competing interests

H.L., J.J. and H-M.H. have filed a patent application titled 'Alumina nanoparticle bioconjugates and methods of stimulating immune response using said bioconjugates'. Y.L. has no competing financial interests.

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Li, H., Li, Y., Jiao, J. et al. Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response. Nature Nanotech 6, 645–650 (2011). https://doi.org/10.1038/nnano.2011.153

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