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Wang, Jiao; Toregrosa-Allen, Sandra; Elzey, Bennett D.; Utturkar, Sagar; Lanman, Nadia Atallah; Bernal-Crespo, Victor; Behymer, Matthew M.; Knipp, Gregory T.; Yun, Yeonhee; Veronesi, Michael C.; Sinn, Anthony L.; Pollok, Karen E.; Brutkiewicz, Randy R.; Nevel, Kathryn S.; Matosevic, Sandro

Multispecific targeting of glioblastoma with tumor microenvironment-responsive multifunctional engineered NK cells

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  • Medientyp: E-Artikel
  • Titel: Multispecific targeting of glioblastoma with tumor microenvironment-responsive multifunctional engineered NK cells
  • Beteiligte: Wang, Jiao; Toregrosa-Allen, Sandra; Elzey, Bennett D.; Utturkar, Sagar; Lanman, Nadia Atallah; Bernal-Crespo, Victor; Behymer, Matthew M.; Knipp, Gregory T.; Yun, Yeonhee; Veronesi, Michael C.; Sinn, Anthony L.; Pollok, Karen E.; Brutkiewicz, Randy R.; Nevel, Kathryn S.; Matosevic, Sandro
  • Erschienen: Proceedings of the National Academy of Sciences, 2021
  • Erschienen in: Proceedings of the National Academy of Sciences
  • Sprache: Englisch
  • DOI: 10.1073/pnas.2107507118
  • ISSN: 1091-6490; 0027-8424
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Significance</jats:title><jats:p>Glioblastoma (GBM) is the most aggressive brain cancer and highly resistant to therapy, including immunotherapies. It is able to escape immune recognition due to its high heterogeneity, active immunometabolic suppression, and antigen escape mechanisms. Here, we describe an immunotherapy centered around human natural killer (NK) cells engineered to simultaneously target these pathways of immune resistance. These engineered NK cells are able to block adenosine signaling in GBM via CD73 while avoiding antigen escape. We also uncover the functional cooperation between these cells’ intratumoral infiltration and impaired autophagy in GBM as a powerful approach to traffick NK cells into the GBM niche. This NK cell–based immunotherapy provides opportunities to broaden the breadth and versatility of current therapeutic regimens for GBM.</jats:p>
  • Zugangsstatus: Freier Zugang