ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Engineering CAR T Cells for Hepatocellular Carcinoma Recurrence after Liver Transplantation.bioRxiv : the preprint server for biology · 2026Article
- Systematic Review of Immunosuppression After Chimeric Antigen Receptor T-Cell Therapy for Posttransplant Lymphoproliferative Disorder.Kidney international reports · 2026Article
- Engineering human Tregs to resist tacrolimus via FKBP12 gene editing.Frontiers in immunology · 2026Article
- HLA incompatibility mitigation strategies in off-the-shelf cancer immunotherapies: clinical implications and a practical framework for strategy selection and combination.Frontiers in immunology · 2026Article
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- Advances in mechanistic investigation and treatment of steroid-refractory ICI-induced liver injury.Clinical and experimental medicine · 2025Review
- Multiplex engineering and multifunction T cells for precise and effective immunotherapies.Frontiers in immunology · 2025Review
- Engineering a solution for allogeneic CAR-T rejection.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Abstract
Chimeric antigen receptor (CAR) T cells from allogeneic donors promise "off-the-shelf" availability by overcoming challenges associated with autologous cell manufacturing. However, recipient immunologic rejection of allogeneic CAR-T cells may decrease their in vivo lifespan and limit treatment efficacy. Here, we demonstrate that the immunosuppressants rapamycin and tacrolimus effectively mitigate allorejection of HLA-mismatched CAR-T cells in immunocompetent humanized mice, extending their in vivo persistence to that of syngeneic humanized mouse-derived CAR-T cells. In turn, genetic knockout (KO) of FKBP prolyl isomerase 1A (FKBP1A), which encodes a protein targeted by both drugs, was necessary to confer CD19-specific CAR-T cells (19CAR) robust functional resistance to these immunosuppressants. FKBP1A
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