한빛사논문
Hyun Young Shin1, Seil Jang1, Hyeong Jung Woo2, Jae-Hee Chung1, Woon-Hae Kim1, Dongoh Kim1, Minju Kang1, Yujin Lim1, Omer Habib1, Jungmin Lee1, Sohae Yang2, Dae Hee Lee1, Minseok S. Kim1,2,3,4
1CTCELLS Inc., 216, Gaepo-ro, Gangnam-gu, Seoul, 06307, Republic of Korea
2Department of New Biology, DGIST, Daegu, 42988, Republic of Korea
3Translational Responsive Medicine Center (TRMC), DGIST, Daegu 42988, Republic of Korea
4New Biology Research Center (NBRC), DGIST, Daegu 42988, Republic of Korea
H.Y.S and S.J contributed equally to this work.
Corresponding author: Minseok S. Kim
Abstract
Natural killer (NK) cells are an attractive cell source in cancer immunotherapy due to their potent antitumor ability and promising safety for allogenic applications. However, the clinical outcome of NK cell therapy has been limited due to poor persistence and loss of activity in the cytokine-deficient tumor microenvironment. Benefits from exogenous administration of soluble interleukin-2 (IL-2) to stimulate the activity of NK cells have not been significant due to cytokine consumption and activation of other immune cells, compromising both efficacy and safety.
Methods: To overcome these drawbacks, we developed a novel membrane-bound protein (MBP) technology to express IL-2 on the surface of NK-92 cells (MBP NK) inducing autocrine signal for proliferation without IL-2 supplementation.
Results: The MBP NK cells exhibited not only improved proliferation in IL-2 deficient conditions but also stronger secretion of cytolytic granules leading to enhanced anti-tumor activity both in vitro and in vivo. Furthermore, the experiment with a spheroid solid tumor model exhibited enhanced infiltration by MBP NK cells creating higher local effector-to-target ratio for efficient tumor killing. These results suggest MBP technology can be an effective utility for NK-92 cell engineering to increase anti-tumor activity and reduce potential adverse effects, providing a higher therapeutic index in clinical applications.
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