Version 1
: Received: 8 July 2024 / Approved: 9 July 2024 / Online: 10 July 2024 (04:13:17 CEST)
How to cite:
Grahnert, A.; Seiffert, S.; Wenk, K.; Schmiedel, D.; Boldt, A.; Vucinic, V.; Merz, M.; Platzbecker, U.; Klemann, C.; Ulrike, K.; Friedrich, M. Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring After BiTEs/bsAbs and CAR T-cell Pretreatment.. Preprints2024, 2024070787. https://doi.org/10.20944/preprints202407.0787.v1
Grahnert, A.; Seiffert, S.; Wenk, K.; Schmiedel, D.; Boldt, A.; Vucinic, V.; Merz, M.; Platzbecker, U.; Klemann, C.; Ulrike, K.; Friedrich, M. Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring After BiTEs/bsAbs and CAR T-cell Pretreatment.. Preprints 2024, 2024070787. https://doi.org/10.20944/preprints202407.0787.v1
Grahnert, A.; Seiffert, S.; Wenk, K.; Schmiedel, D.; Boldt, A.; Vucinic, V.; Merz, M.; Platzbecker, U.; Klemann, C.; Ulrike, K.; Friedrich, M. Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring After BiTEs/bsAbs and CAR T-cell Pretreatment.. Preprints2024, 2024070787. https://doi.org/10.20944/preprints202407.0787.v1
APA Style
Grahnert, A., Seiffert, S., Wenk, K., Schmiedel, D., Boldt, A., Vucinic, V., Merz, M., Platzbecker, U., Klemann, C., Ulrike, K., & Friedrich, M. (2024). Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring After BiTEs/bsAbs and CAR T-cell Pretreatment.. Preprints. https://doi.org/10.20944/preprints202407.0787.v1
Chicago/Turabian Style
Grahnert, A., Koehl Ulrike and Maik Friedrich. 2024 "Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring After BiTEs/bsAbs and CAR T-cell Pretreatment." Preprints. https://doi.org/10.20944/preprints202407.0787.v1
Abstract
For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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