In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma.
J Exp Clin Cancer Res
; 43(1): 262, 2024 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-39272178
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoterapia Adotiva
/
Linfoma de Células T
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Modelos Animais de Doenças
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Receptores de Antígenos Quiméricos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Exp Clin Cancer Res
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
Reino Unido