Academic Journal
Mutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemia
| العنوان: | Mutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemia |
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| المؤلفون: | Märkl, Florian, Ali Khan, Murtaza, Paschold, Lisa, Zhang, Tianjiao, und viele weitere |
| سنة النشر: | 2024 |
| المجموعة: | Share it - Open Access und Forschungsdaten-Repositorium der Hochschulbibliotheken in Sachsen-Anhalt |
| مصطلحات موضوعية: | ddc:610 |
| الوصف: | The concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer. B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor-specific-stereotyped sequences in the form of point mutations that drive self-engagement of the BCR and autologous signaling. Here, we use a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. We develop murine and humanized CAR constructs expressed in T cells from healthy donors and CLL patients that eradicate IGLV3-21R110 expressing cell lines and primary CLL cells, but neither cells expressing the non-pathogenic IGLV3-21G110 light chain nor polyclonal healthy B cells. In vivo experiments confirm epitope-selective cytolysis in xenograft models in female mice using engrafted IGLV3-21R110 expressing cell lines or primary CLL cells. We further demonstrate in two humanized mouse models lack of cytotoxicity towards human B cells. These data provide the basis for advanced approaches of resistance-preventive and biomarker-guided cellular targeting of functionally relevant lymphoma driver mutations sparing normal B cells. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-1-885308-85-6 1-885308-85-X |
| Relation: | 188530885X; http://dx.doi.org/10.25673/115596 |
| DOI: | 10.25673/115596 |
| الاتاحة: | https://opendata.uni-halle.de//handle/1981185920/117549 https://doi.org/10.25673/115596 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.AC94F2FB |
| قاعدة البيانات: | BASE |
| ردمك: | 9781885308856 188530885X |
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| DOI: | 10.25673/115596 |