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A carbon nanotube–polymer composite for T-cell therapy

Nature Nanotechnology volume 9, pages 639–647 (2014)Cite this article

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A Corrigendum to this article was published on 03 September 2014

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Abstract

Clinical translation of cell therapies requires strategies that can manufacture cells efficiently and economically. One promising way to reproducibly expand T cells for cancer therapy is by attaching the stimuli for T cells onto artificial substrates with high surface area. Here, we show that a carbon nanotube–polymer composite can act as an artificial antigen-presenting cell to efficiently expand the number of T cells isolated from mice. We attach antigens onto bundled carbon nanotubes and combined this complex with polymer nanoparticles containing magnetite and the T-cell growth factor interleukin-2 (IL-2). The number of T cells obtained was comparable to clinical standards using a thousand-fold less soluble IL-2. T cells obtained from this expansion were able to delay tumour growth in a murine model for melanoma. Our results show that this composite is a useful platform for generating large numbers of cytotoxic T cells for cancer immunotherapy.

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Figure 1: Design of CNPs.
Figure 2: Characterization of CNPs.
Figure 3: CNPs enhance the long-term expansion of CD8+ T cells.
Figure 4: Effect of CNPs on T-cell phenotype and cytolytic activity.
Figure 5: Adoptive immunotherapy with CNP-expanded T cells delays the growth of tumours in a murine melanoma model.
Figure 6: Expansion of human T cells using CNPs.

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  • 14 August 2014

    In the version of this Article previously published, the name of the co-author Kevan C. Herold was spelt incorrectly. This has now been corrected in the online versions of the Article.

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Acknowledgements

This work was supported in part by a National Science Foundation Career Award (0747577) to T.M.F. and in part by a National Institutes of Health Autoimmunity Center of Excellence Pilot Award (U19 AI056363, to T.M.F. and K.H.) and a Yale Specialized Programs of Research Excellence (SPORE) Investigator Pilot Award (to T.M.F.) and in part by the Yale SPORE in Skin Cancer (grant no. 1 P50 CA121974). The authors thank J. Alderman and R. Flavell for helpful critique, and M. Sznol, R. Tigelaar and M. Bosenberg (Yale Cancer Center), as well as P. De Sousa (University of Edinburgh), for technical comments regarding adoptive therapy. The authors also thank P. Van Tassel for technical advice regarding CNT preparation.

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Author notes

  1. Nalini Vudattu and Justin Garyu: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemical Engineering, Yale University, New Haven, PO Box 208284, Connecticut 06511, USA

    Tarek R. Fadel, Nan Li, Gary L. Haller, Lisa D. Pfefferle & Tarek M. Fahmy

  2. Department of Biomedical Engineering, Yale University, New Haven, PO Box 208284, Connecticut 06511, USA

    Fiona A. Sharp, Ragy Ragheb, Dongin Kim, Enping Hong & Tarek M. Fahmy

  3. Department of Immunobiology and Internal Medicine, Yale University, New Haven, PO Box 208284, Connecticut 06520, USA

    Nalini Vudattu, Justin Garyu, Kevan C. Herold & Tarek M. Fahmy

  4. Department of Immunobiology and Microbiology, Blegdamsvej 3b DK2200, Copenhagen N, Denmark

    Sune Justesen

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Contributions

T.R.F. and T.M.F. designed all of the experiments for this study. R.R synthesized the magnetite and fabricated the polymer nanoparticles. N.L. synthesized the carbon nanotubes. S.J. synthesized the biotinylated MHC-I. T.R.F., L.D.P. and G.L.H. characterized the carbon nanotubes. T.R.F. and R.R. characterized the particles and the CNP system. R.R. characterized the magnetic properties of the PLGA nanoparticles and CNPs. T.R.F. performed inverted, fluorescence and FRET imaging. T.R.F. performed in vitro characterization experiments and FACS analyses. T.R.F., F.S. and E.H. performed the studies on T-cell cytotoxicity. T.R.F., F.S. and D.K. characterized the tumour-infiltrating lymphocytes. F.S., N.V., and J.G. performed the human T cell expansion experiments. T.R.F. and D.K. performed the in vivo experiments. T.M.F. conceived the formulations. T.R.F. wrote the manuscript. T.M.F., R.R., D.K., F.S., E.H., L.D.P., and K.C.H. edited the manuscript.

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Correspondence to Tarek M. Fahmy.

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The authors declare no competing financial interests.

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Fadel, T., Sharp, F., Vudattu, N. et al. A carbon nanotube–polymer composite for T-cell therapy. Nature Nanotech 9, 639–647 (2014). https://doi.org/10.1038/nnano.2014.154

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