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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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Main Authors: Liu, Yi (Author) , Lauk, Annika (Author) , Sedloev, David (Author) , Brysting, Josephine (Author) , Cetin, Ela (Author) , Liu, Chunan (Author) , Mönnig, Maximilian (Author) , Luft, Thomas (Author) , Yun, Haiyang (Author) , Schmitt, Michael (Author) , Sauer, Tim (Author) , Zhou, Fengbiao (Author) , Rohde, Christian (Author) , Müller-Tidow, Carsten (Author)
Format: Article (Journal)
Language:English
Published: 15 February 2026
In: International journal of cancer
Year: 2026, Volume: 158, Issue: 4, Pages: 994-1007
ISSN:1097-0215
DOI:10.1002/ijc.70146
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.70146
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.70146
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Author Notes: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
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Summary: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.
Item Description:Online verfügbar am 2. Oktober 2025
Gesehen am 27.01.2026
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.70146

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