Micropatterned nickel titanium (commonly known as nitinol) thin films with complex designs, high structural resolution and excellent biocompatibility can be cheaply fabricated using magnetron sputtering. Here, we show that these benefits can be leveraged to fabricate micromesh implants that are loaded with tumour-specific human chimeric antigen receptor (CAR)-T cells for the treatment of solid tumours. In a mouse model of non-resectable ovarian cancer, the cell-loaded nitinol thin films spatially conformed to the implantation site, fostered the rapid expansion of T cells, delivered a high density of T cells directly to the tumour and significantly improved animal survival. We also show that self-expandable stents that were coated with T-cell-loaded films and implanted into subcutaneous tumours in mice improved the duration of stent patency by delaying tumour ingrowth. By providing direct access to tumours, CAR-T-cell-loaded micropatterned nitinol thin films can improve the effects of cell-based therapies.
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The authors declare that all data supporting the findings of this study are provided within the paper and the Supplementary Information.
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This work was supported in part by the Fred Hutchinson Cancer Research Center’s Immunotherapy Initiative, with funds provided by the Bezos Family Foundation.
The Fred Hutchinson Cancer Center and M.T.S. have filed a patent pertaining to TFN-based micromeshes and stents for the delivery of tumour-specific T cells (PCT/US2017/067965), which was licensed by Monarch Biosciences. The other authors declare no competing interests.
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Coon, M.E., Stephan, S.B., Gupta, V. et al. Nitinol thin films functionalized with CAR-T cells for the treatment of solid tumours. Nat Biomed Eng 4, 195–206 (2020). https://doi.org/10.1038/s41551-019-0486-0
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