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: | , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
15 February 2026
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| 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 |
| 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 |
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| 520 | |a 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. | ||
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