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A three-dimensional hyaluronic acid-based niche enhances the therapeutic efficacy of human natural killer cell-based cancer immunotherapy. | LitMetric

A three-dimensional hyaluronic acid-based niche enhances the therapeutic efficacy of human natural killer cell-based cancer immunotherapy.

Biomaterials

Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea; Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea. Electronic address:

Published: July 2020

AI Article Synopsis

  • The adoptive transfer of natural killer (NK) cells is gaining prominence in cancer immunotherapy, with a focus on enhancing targeting through engineered chimeric antigen receptors (CARs).
  • A new method called 3D-ENHANCE, which uses a hyaluronic acid-based three-dimensional niche for cell expansion, outperforms traditional two-dimensional culture techniques by improving NK cell characteristics and tumor-fighting abilities.
  • In vivo testing showed that using 3D-ENHANCE around the surgical site significantly reduces the chance of cancer recurrence and metastasis after tumor removal, highlighting its potential for better post-surgical outcomes.

Article Abstract

Adoptive transfer of natural killer (NK) cells is becoming one of the most important parts of cancer immunotherapy. However, recent accomplishments have focused on the improvement of the targeting effects based on the engineering of chimeric antigen receptors (CARs) on cell surfaces. Despite the large quantity of therapeutic cells required for clinical applications, the technology for ex vivo expansion is not well developed. Herein, a three-dimensional (3D) engineered hyaluronic acid-based niche for cell expansion (3D-ENHANCE) is introduced. Compared with the conventional two-dimensional (2D) method, NK-92 cell lines and human EGFR-specific (CAR)-NK cells cultured in 3D-ENHANCE yield favorable mRNA expressions, elevated cytokine release, upregulated proliferative and tumor-lytic abilities, and result in enhanced antitumor efficacy. Furthermore, controllable degradation rates can be realized by tuning the formulation of 3D-ENHANCE so that it can be applied as an implantable cell reservoir at surgical sites. In vivo results with the incompletely resected MDA-MB-231 model confirm that the peri-operative implantation of 3D-ENHANCE prevents the relapse and metastases after surgery. Overall, 3D-ENHANCE presents an effective cytokine-free niche for ex vivo expansion and postsurgical treatment that enhances the low-therapeutic efficacy of human NK cells.

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Source
http://dx.doi.org/10.1016/j.biomaterials.2020.119960DOI Listing

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