Knelangen, Nele and Bader, Ulrika and Maniaki, Evangelia and Langan, Patricia S. and Engert, Fabian and Drees, Britta and Schwarzer, Juliane and Kotter, Bettina and Kiefer, Lukas and Gattinoni, Luca and Engels, Boris and Mittelstaet, Joerg and Webster, Brian (2025) CAR T cells re-directed by a rationally designed human peptide tag demonstrate efficacy in preclinical models. CYTOTHERAPY, 27 (9). pp. 1094-1104. ISSN 1465-3249, 1477-2566
Full text not available from this repository. (Request a copy)Abstract
Currently, only a few chimeric antigen receptor (CAR) T cell therapies have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of B-cell malignancies. To enable broader application of the CAR T cell technology in other indications, improved control and flexible targeting of multiple tumor antigens are required. Here, we developed a novel adapter CAR (AdCAR) T cell platform for flexible targeting of multiple tumor antigens. This platform is based on a short peptide tag derived from an interdomain region of fibroblast growth factor receptor 2 (FGFR2), commonly mutated in cancer. To select AdCARs specific for mutated FGFR2-derived peptide tags, a multistep pooled screening approach in primary T cells was employed, incorporating MACS separation and next-generation sequencing. The resulting AdCAR was highly specific for the FGFR2-derived peptide tag. Using different in vitro and in vivo model systems, the activity of AdCAR T cells was shown to be strictly dependent on the presence of the adapter and corresponding target antigen. Moreover, AdCAR T cells could be redirected to different target antigens by the addition of respective adapter molecules (AM). Finally, in situ expression of functional AM in primary T cells under control of a drug-inducible promoter system was demonstrated, highlighting the potential for controlling the activity of AdCAR T cells by cellular micropharmacies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FGFR2 MUTATIONS; SAFETY SWITCH; IN-VIVO; ANTIGEN; CANCER; IMMUNOTHERAPY; UNICAR-T-CD123; REMISSIONS; ACTIVATION; DEPLETION; adapter CART cell; CART cell; immunotherapy; micropharmacy; universal CAR |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Sep 2026 08:24 |
| Last Modified: | 23 Sep 2026 08:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66865 |
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