Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Monarch Biosciences, Inc., Los Angeles, CA, USA.
Nat Biomed Eng. 2020 Feb;4(2):195-206. doi: 10.1038/s41551-019-0486-0. Epub 2019 Dec 9.
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.
采用磁控溅射技术,可廉价地制造出具有复杂设计、高结构分辨率和出色生物相容性的微图案镍钛(通常称为镍钛诺)薄膜。在这里,我们展示了这些优势可用于制造负载肿瘤特异性嵌合抗原受体 (CAR)-T 细胞的微网植入物,以治疗实体瘤。在无法切除的卵巢癌小鼠模型中,负载细胞的镍钛诺薄膜与植入部位空间贴合,促进了 T 细胞的快速扩增,将高浓度的 T 细胞直接递送到肿瘤部位,并显著提高了动物的存活率。我们还表明,涂有负载 T 细胞的薄膜的自扩张支架并植入小鼠的皮下肿瘤中,通过延迟肿瘤侵入来延长支架通畅时间。通过提供对肿瘤的直接访问,负载 CAR-T 细胞的微图案镍钛诺薄膜可以提高细胞疗法的效果。
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