한빛사논문
Young Ha Ahna, Long Rene, Seok Min Kima,b, Sang-Hwan Seoa, Cho-Rok Jungc, Da Seul Kima, Ji-Yoon Noha, Soo Yun Leea, Hyun Seung Leed, Mi Young Chod, Haiyoung Junga, Suk Ran Yoona, Jung-Eun Kime, Sang Nam Leee, Sohyun Kime, Il Woo Shine, Hong Sik Shine, Kwan Soo Hongd, Yong Taik Lime,*, Inpyo Choia,*, Tae-Don Kima,b,*
aImmunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
bDepartment of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea
cStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
dBioimaging Research Team, Korea Basic Science Institute ochang center (KBSI), Yeongudanji-ro, cheongwon-gu, Cheongju, chungcheongbuk-do, 28119, Republic of Korea
eSKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Engineering, and School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea
*Correspondence to Yong Taik Lim, Inpyo Choi, Tae-Don Kim
Y. H. Ahn, L. Ren, and S. M. Kim contributed equally to this work.
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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