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Background <p>Neurofibromatosis 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.</p> Methods <p>AXL-CAR-T cells, containing an anti-AXL single-chain variable fragment, were derived from NF1 patients (<i>n</i> = 27) and healthy donors (<i>n</i> = 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.</p> Results <p>AXL-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.</p> Conclusions <p>NF1 patient-derived AXL-CAR-T cells demonstrated similar quality and efficacy to those from healthy donors, supporting their potential autologous therapy for MPNST.</p>

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Evaluating CAR-T cells from neurofibromatosis type 1 (NF1) patients for targeting AXL in malignant peripheral nerve sheath tumors associated with NF1

  • 期刊论文

  • 发表日期：

    2025年9月1日

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  • Po-Yuan Huang,
  • I-An Shih,
  • Ying-Chih Liao,
  • Chien-Ting Lin,
  • Huey-Ling You,
  • Ming-Jen Lee

摘要

Background

Neurofibromatosis 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.

Methods

AXL-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.

Results

AXL-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.

Conclusions

NF1 patient-derived AXL-CAR-T cells demonstrated similar quality and efficacy to those from healthy donors, supporting their potential autologous therapy for MPNST.