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차의과학대학교

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J. Control. Release, Feb 08 2024, S0168-3659(24)00095-6 | https://doi.org/10.1016/j.jconrel.2024.02.008 Nano-chemical priming strategy to enhance TGF-β resistance and anti-tumor activity of natural killer cells

Seung Hee Choi ¹, Hui Bang Cho ¹, Jin-Ho Choi, Hye Jin Kim, Hye Jung Jang, Seohyun Cho, Eunchong Maeng, Hail Park, Ki Seo Ryu, Keun-Hong Park, Kyung-Soon Park

Department of Biomedical Science, CHA University, Seongnam-si, Republic of Korea

¹These authors equally contributed to this work.

Corresponding authors : Keun-Hong Park, Kyung-Soon Park

Abstract

Immunotherapy based on adoptive transfer of natural killer (NK) cells is a promising strategy for circumventing the limitations of cancer treatments. However, components of the immunosuppressive tumor microenvironment (TME), such as transforming growth factor-beta (TGF-β), compromise the therapeutic efficacy of NK cells significantly. To address these limitations, we developed a novel method of engineering NK cells for adaptive transfer. The method is based on nanogels that serve two functions: (1) they overcome the TGF-β-mediated stress environment of the TME, and (2) they enhance the direct anti-tumor activity of NK cells. Previously, we demonstrated that cationic compounds such as 25 K branched polyethylenimine (25 K bPEI) prime NK cells, putting them in a 'ready-to-fight' state. Based on these findings, we designed nanogels that have two primary characteristics: (1) they encapsulate galunisertib (Gal), which is used clinically to inhibit TGF-β receptor activity, thereby blocking TGF-β signaling; and (2) they provide cells with a surface coating of 25 K bPEI. When grown in culture medium containing TGF-β, nanogel-treated NK cells demonstrated greater migration ability, degranulation activity, and cytotoxicity towards cancer cells than untreated NK cells. Additionally, the in vivo efficacy of nanogel-treated NK cells against PC-3 xenografts was significantly greater than that of Chem_NK cells primed by 25 K bPEI alone. These findings suggest that Gal-loaded 25 K bPEI-coated nanogels exert anti-tumor effects via chemical priming, as well suppressing the effects of TGF-β on NK cells. We also expect 25 K bPEI-based nanogels to have great potential to overcome the suppressive effects of the TME through their NK cell-priming activity and delivery of the desired chemicals.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-20)
연구진국내 연구진
분야 생명과학 > 면역학

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