Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity

Shin, Hyun Young; Jang, Seil; Woo, Hyeong Jung; Chung, Jae-Hee; Kim, Woon-Hae; Kim, Dongoh; Kang, Minju; Lim, Yujin; Habib, Omer; Lee, Jungmin; Yang, Sohae; Lee, Dae Hee; Kim, Minseok S.

doi:10.7150/thno.79942

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2023; 13(5):1506-1519. doi:10.7150/thno.79942 This issue Cite

Research Paper

Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity

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. Kim^1,2,3,4✉

1. CTCELLS Inc., 216, Gaepo-ro, Gangnam-gu, Seoul, 06307, Republic of Korea
2. Department of New Biology, DGIST, Daegu, 42988, Republic of Korea
3. Translational Responsive Medicine Center (TRMC), DGIST, Daegu 42988, Republic of Korea
4. New Biology Research Center (NBRC), DGIST, Daegu 42988, Republic of Korea

Citation:

Shin HY, Jang S, Woo HJ, Chung JH, Kim WH, Kim D, Kang M, Lim Y, Habib O, Lee J, Yang S, Lee DH, Kim MS. Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity. Theranostics 2023; 13(5):1506-1519. doi:10.7150/thno.79942. https://www.thno.org/v13p1506.htm

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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.

Keywords: natural killer cell, membrane-bound protein (MBP), interleukin-2, self-activation, tumor-infiltrating lymphocytes, microwell array chip

Citation styles

APA

Shin, H.Y., Jang, S., Woo, H.J., Chung, J.H., Kim, W.H., Kim, D., Kang, M., Lim, Y., Habib, O., Lee, J., Yang, S., Lee, D.H., Kim, M.S. (2023). Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity. Theranostics, 13(5), 1506-1519. https://doi.org/10.7150/thno.79942.

ACS

Shin, H.Y.; Jang, S.; Woo, H.J.; Chung, J.H.; Kim, W.H.; Kim, D.; Kang, M.; Lim, Y.; Habib, O.; Lee, J.; Yang, S.; Lee, D.H.; Kim, M.S. Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity. Theranostics 2023, 13 (5), 1506-1519. DOI: 10.7150/thno.79942.

NLM

CSE

Shin HY, Jang S, Woo HJ, Chung JH, Kim WH, Kim D, Kang M, Lim Y, Habib O, Lee J, Yang S, Lee DH, Kim MS. 2023. Cytokine engineered NK-92 therapy to improve persistence and anti-tumor activity. Theranostics. 13(5):1506-1519.

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