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

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 lar...

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Bibliographic Details
Published in:Biomaterials 2020-07, Vol.247, p.119960-119960, Article 119960
Main Authors: Ahn, Young Ha, Ren, Long, Kim, Seok Min, Seo, Sang-Hwan, Jung, Cho-Rok, Kim, Da Seul, Noh, Ji-Yoon, Lee, Soo Yun, Lee, Hyunseung, Cho, Mi Young, Jung, Haiyoung, Yoon, Suk Ran, Kim, Jung-Eun, Lee, Sang Nam, Kim, Sohyun, Shin, Il Woo, Shin, Hong Sik, Hong, Kwan Soo, Lim, Yong Taik, Choi, Inpyo, Kim, Tae-Don
Format: Article
Language:English
Subjects:
Adoptive cell transfer
Cancer immunotherapy
Cell Line, Tumor
Cytotoxicity, Immunologic
Humans
Hyaluronic Acid
Immunotherapy
Immunotherapy, Adoptive
Killer Cells, Natural
Natural killer cells
Neoplasms - therapy
Scaffold
Three-dimensional culture
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2020.119960