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Integrated scFv identification and CAR T cell generation for AML targeting in vivo

Cancer immunotherapy has witnessed remarkable advancements, particularly in the development of chimeric antigen receptor (CAR) T cell therapy. Here, we integrated single chain variable fragment (scFv) development with CAR T cell generation based on a newly developed scFv phagemid library. High-throu...

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Hauptverfasser: Liu, Yi (VerfasserIn) , Lauk, Annika (VerfasserIn) , Sedloev, David (VerfasserIn) , Brysting, Josephine (VerfasserIn) , Cetin, Ela (VerfasserIn) , Liu, Chunan (VerfasserIn) , Mönnig, Maximilian (VerfasserIn) , Luft, Thomas (VerfasserIn) , Yun, Haiyang (VerfasserIn) , Schmitt, Michael (VerfasserIn) , Sauer, Tim (VerfasserIn) , Zhou, Fengbiao (VerfasserIn) , Rohde, Christian (VerfasserIn) , Müller-Tidow, Carsten (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 February 2026
In: International journal of cancer
Year: 2026, Jahrgang: 158, Heft: 4, Pages: 994-1007
ISSN:1097-0215
DOI:10.1002/ijc.70146
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.70146
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.70146
Volltext
Verfasserangaben:Yi Liu, Annika Lauk, David Sedloev, Josephine Brysting, Ela Cetin, Chunan Liu, Maximilian Mönnig, Thomas Luft, Haiyang Yun, Michael Schmitt, Tim Sauer, Fengbiao Zhou, Christian Rohde, Carsten Müller-Tidow
Beschreibung
Zusammenfassung:Cancer immunotherapy has witnessed remarkable advancements, particularly in the development of chimeric antigen receptor (CAR) T cell therapy. Here, we integrated single chain variable fragment (scFv) development with CAR T cell generation based on a newly developed scFv phagemid library. High-throughput long-read PacBio sequencing identified 4.5 × 107 unique full-length scFv proteins within the generated library. As a proof of principle, we screened for scFvs targeting C-type lectin-like molecule-1 (CLL1) with subsequent cloning into a third generation retroviral CAR backbone. Functional assays revealed the specificity and potency of these CAR T cells in targeting CLL1-positive AML cells in vitro. In vivo studies reduced tumor burden and improved survival rates compared to controls. Taken together, screening for tumor-specific scFvs against CLL1 can rapidly generate AML-specific CAR T cells with effective tumor killing in vivo.
Beschreibung:Online verfügbar am 2. Oktober 2025
Gesehen am 27.01.2026
Beschreibung:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.70146

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