Nitinol thin films functionalized with CAR-T cells for the treatment of solid tumours

Nat Biomed Eng. 2020 Feb;4(2):195-206. doi: 10.1038/s41551-019-0486-0. Epub 2019 Dec 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloys*
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Humans
  • Immunotherapy, Adoptive / instrumentation*
  • Immunotherapy, Adoptive / methods*
  • Infusion Pumps, Implantable*
  • Mice
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy*
  • Receptors, Chimeric Antigen / therapeutic use*
  • T-Lymphocytes / physiology

Substances

  • Alloys
  • Receptors, Chimeric Antigen
  • nitinol