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The SpyCatcher-SpyTag interaction mediates tunable anti-tumor cytotoxicity of NK cells.
Guo, Changjiang; Guo, Xiali; Li, Xiaojuan; Dong, Meng; Wang, Xiang; Cheng, Shizhuang; Zhi, Lingtong; Niu, Zhiyuan; Zhu, Wuling.
Afiliación
  • Guo C; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China. Electronic address: changjiangguo@xxmu.edu.cn.
  • Guo X; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
  • Li X; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
  • Dong M; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
  • Wang X; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
  • Cheng S; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
  • Zhi L; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
  • Niu Z; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
  • Zhu W; Henan Province Engineering Research Center of Innovation for Synthetic Biology, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China. Electronic address: wuling_zhu@163.com.
Mol Immunol ; 165: 11-18, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38128392
ABSTRACT
Chimeric antigen receptor (CAR)-modified T and NK cell immunotherapy is a promising approach for cancer treatment. Due to the lack of tunability in anti-tumor activity, conventional CAR therapies have limited efficacy at low tumor antigen densities. To tune the CAR response to tumor cell surface antigens, we have developed a split CAR using the SpyCatcher-SpyTag system. The SpyCatcher serves as the ectodomain to constitute a SpyCatcher-CAR (SpyCAR), while SpyTag is attached to the antibodies that recognize tumor antigens. With dimerization mediated by SpyCatcher and SpyTag, the number and activation level of SpyCARs recruited by tumor antigens depends on the SpyTag number in the "antibody-SpyTag" fusion protein. The results demonstrated that the increasing number of SpyTags effectively enhanced the cytotoxicity of SpyCAR-NK92 cells against target cells. The development of SpyCAR with tunable cytotoxicity provides a novel strategy for CAR-based tumor immunotherapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Límite: Humans Idioma: En Revista: Mol Immunol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Límite: Humans Idioma: En Revista: Mol Immunol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido