KEY TAKEAWAYS
- The study aimed to investigate the efficacy of in vivo generated CAR T cell therapy as a novel treatment for AITL using a murine model.
- Researchers noticed that in vivo generated CAR T cells present a promising new therapeutic option for patients with CD4-driven T cell lymphomas.
For angioimmunoblastic T cell lymphoma (AITL), a rare malignancy, specific treatment options are lacking, leading to poor survival outcomes. They have previously established a murine model that closely resembles human AITL, enabling the evaluation of novel therapies. In both human and murine AITL, CD4+ follicular helper T (Tfh) cells play a pivotal role in driving the disease. Consequently, chimeric antigen receptor (CAR) T cell therapy emerges as a potential new therapeutic strategy.
Adrien Krug and the team aimed to assess the efficacy of in vivo generated CAR T cells for the treatment of AITL.
They performed an inclusive analysis to prevent fratricide among CAR T cells when delivering a CD4-specific CAR by employing a lentiviral vector (LV) encoding an anti-CD4 CAR. This approach facilitated exclusive entry into CD8 T cells, ensuring targeted therapy without affecting the CD4+ T cell population.
The high CAR expression levels in CD8 T cells were achieved by anti-CD4 CAR CD8-targeted LVs within murine AITL biopsies. Malignant CD4+ Tfh cells were effectively eliminated from the mAITL lymphoma, while the CAR+ CD8 T cells expanded upon interaction with the CD4 receptor and developed into functional cytotoxic cells.
Ultimately, the in vivo injection of the CAR+ CD8 LVs into the preclinical AITL mouse model bearing lymphomas significantly prolonged survival. Furthermore, the in vivo generated functional CAR+ CD8 T cells efficiently diminished neoplastic T cell numbers within the mAITL tumors.
The study concluded that in vivo generated CAR T cells represent a pioneering approach for the treatment of T cell lymphomas. This innovative strategy provides a novel therapeutic option for patients suffering from CD4-driven T cell malignancies, potentially improving outcomes in this challenging disease.
This study was funded by the ‘Fondation ARC pour la Recherche sur le Cancer’, la Ligue Nationale Contre le Cancer “Equipe Labellisée”, the Agence Nationale de la Recherche’ (Labex SIGNALIFE ANR-11-LABX-0028–01), IDEX UCAJedi ANR-15-IDEX- 01 by ANR ANR-16-CE16-0024–01, la Ville de Nice, the Canceropôle PACA, Institut National du Cancer (INCA).
Source: https://pubmed.ncbi.nlm.nih.gov/39272178/
Krug A, Saidane A, Martinello C, et al. (2024). “In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma.” J Exp Clin Cancer Res. 2024;43(1):262. Published 2024 Sep 14. doi:10.1186/s13046-024-03179-5
