Bibliographic Details
| Title: |
In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma |
| Authors: |
Adrien Krug, Aymen Saidane, Chiara Martinello, Floriane Fusil, Alexander Michels, Christian J. Buchholz, Jean-Ehrland Ricci, Els Verhoeyen |
| Source: |
Journal of Experimental & Clinical Cancer Research, Vol 43, Iss 1, Pp 1-18 (2024) |
| Publisher Information: |
BMC, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
CD8-targeted virus envelope, CAR T, AITL, In vivo gene therapy, Pseudotyping, Lentiviral vector, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Abstract Background For angioimmunoblastic T cell lymphoma (AITL), a rare cancer, no specific treatments are available and survival outcome is poor. We previously developed a murine model for AITL that mimics closely human disease and allows to evaluate new treatments. As in human AITL, the murine CD4+ follicular helper T (Tfh) cells are drivers of the malignancy. Therefore, chimeric antigen receptor (CAR) T cell therapy might represent a new therapeutic option. Methods To prevent fratricide among CAR T cells when delivering an CD4-specific CAR, we used a lentiviral vector (LV) encoding an anti-CD4 CAR, allowing exclusive entry into CD8 T cells. Results These anti-CD4CAR CD8-targeted LVs achieved in murine AITL biopsies high CAR-expression levels in CD8 T cells. Malignant CD4 Tfh cells were eliminated from the mAITL lymphoma, while the CAR + CD8 T cells expanded upon encounter with the CD4 receptor and were shaped into functional cytotoxic cells. Finally, in vivo injection of the CAR + CD8-LVs into our preclinical AITL mouse model carrying lymphomas, significantly prolonged mice survival. Moreover, the in vivo generated functional CAR + CD8 T cells efficiently reduced neoplastic T cell numbers in the mAITL tumors. Conclusion This is the first description of in vivo generated CAR T cells for therapy of a T cell lymphoma. The strategy described offers a new therapeutic concept for patients suffering from CD4-driven T cell lymphomas. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1756-9966 |
| Relation: |
https://doaj.org/toc/1756-9966 |
| DOI: |
10.1186/s13046-024-03179-5 |
| Access URL: |
https://doaj.org/article/daf8777c96c74d378e623fabf71e0eca |
| Accession Number: |
edsdoj.f8777c96c74d378e623fabf71e0eca |
| Database: |
Directory of Open Access Journals |
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