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Challenges in the Development of NK-92 Cells as an Effective Universal Off-the-Shelf Cellular Therapeutic.
Niu, Zhiyuan; Wang, Mengjun; Yan, Yangchun; Jin, Xinru; Ning, Linwei; Xu, Bingqian; Wang, Yanfeng; Hao, Yuekai; Luo, Zhixia; Guo, Changjiang; Zhi, Lingtong; Zhu, Wuling.
Afiliación
  • Niu Z; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Wang M; School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China.
  • Yan Y; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Jin X; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Ning L; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Xu B; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Wang Y; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Hao Y; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Luo Z; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Guo C; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Zhi L; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
  • Zhu W; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan, China.
J Immunol ; 2024 Sep 18.
Article en En | MEDLINE | ID: mdl-39291926
ABSTRACT
The human-derived NK-92 cell-based CAR-NK therapy exhibits inconsistency with overall suboptimal efficacy and rapid in vivo clearance of CAR-NK92 cells in cancer patients. Analysis indicates that although pre-existing IgM in healthy individuals (n = 10) strongly recognizes both NK-92 and CAR-NK92 cells, IgG and IgE do not. However, only a subset of cancer patients (3/8) exhibit strong IgM recognition of these cells, with some (2/8) showing pre-existing IgG recognition. These results suggest a natural immunoreactivity between NK-92 and CAR-NK92 cells and pre-existing human Abs. Furthermore, the therapy's immunogenicity is evidenced by enhanced IgG and IgM recognition postinfusion of CAR-NK92 cells. We also confirmed that healthy plasma's cytotoxicity toward these cells is reduced by complement inhibitors, suggesting that Abs may facilitate the rapid clearance of CAR-NK92 cells through complement-dependent cytotoxicity. Given that NK-92 cells lack known receptors for IgG and IgM, identifying and modifying the recognition targets for these Abs on NK-92 and CAR-NK92 cells may improve clinical outcomes. Moreover, we discovered that the 72nd amino acid of the NKG2D receptor on NK-92 cells is alanine. Previous studies have demonstrated polymorphism at the 72nd amino acid of the NKG2D on human NK cells, with NKG2D72Thr exhibiting a superior activation effect on NK cells compared with NKG2D72Ala. We confirmed this conclusion also applies to NK-92 cells by in vitro cytotoxicity experiments. Therefore, reducing the immunoreactivity and immunogenicity of CAR-NK92 and directly switching NK-92 bearing NKG2D72Ala to NKG2D72Thr represent pressing challenges in realizing NK-92 cells as qualified universal off-the-shelf cellular therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Immunol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Immunol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos