ArticleBritish journal of cancer2025
Evaluating CAR-T cells from neurofibromatosis type 1 (NF1) patients for targeting AXL in malignant peripheral nerve sheath tumors associated with NF1.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by neurofibromas, with 5-13% of patients risk developing malignant peripheral nerve sheath tumors (MPNST). Current treatments for MPNST are largely ineffective. AXL, overexpressed in MPNST, is a potential target for Chimeric Antigen Receptor T (CAR-T) cell therapy. This study evaluates the immunophenotypes, efficacy, and safety of NF1-derived AXL-CAR-T cells in treating MPNST.
methodsAXL-CAR-T cells, containing an anti-AXL single-chain variable fragment, were derived from NF1 patients (n = 27) and healthy donors (n = 15). Immunophenotypes were characterized using CCR7, CD45RA, CD4, and CD8 markers. The cytotoxicity of CAR-T cells was tested in vitro against MPNST cells, and efficacy and safety were evaluated in an MPNST xenograft mouse model. Multiplex immunoassays and ELISA measured cytokines and granzyme b release.
resultsAXL-CAR-T cells from both NF1 patients and healthy donors had a similar partition in stem cell-like memory T cell composition and comparable ex vivo expansion. AXL-CAR-T cells from both groups effectively lysed MPNST cells in vitro. In vivo, tumor volumes in xenograft mice were significantly reduced with no on-target off-tumor toxicity.
conclusionsNF1 patient-derived AXL-CAR-T cells demonstrated similar quality and efficacy to those from healthy donors, supporting their potential autologous therapy for MPNST.
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