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조회576

동국대학교

Small, Dec 31 2023, | https://doi.org/10.1002/smll.202306738 Surface Engineering of Natural Killer Cells with CD44-targeting Ligands for Augmented Cancer Immunotherapy

Sungjun Kim ¹, Shujin Li ², Ashok Kumar Jangid ¹, Hee Won Park ¹, Dong-Joon Lee ^2,3, Han-Sung Jung ², Kyobum Kim ¹

¹Department of Chemical & Biochemical Engineering, Dongguk University, 30, Pildong-ro 1-gil, Jung-gu, Seoul, 04620, Republic of Korea.

²Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

³Department of Oral Histology, Dankook University College of Dentistry, 119, Dandae-ro, Dongnam-gu, Cheonan, 31116, Chungcheongnam-do, Republic of Korea.

S.K. and S.L. contributed equally to this work.

CORRESPONDING AUTHORS : Han-Sung Jung, Kyobum Kim

Abstract

Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the "recognition-activation" mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2024-01-03)
연구진국내 연구진
분야 생명과학 > 생물공학

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