ArticleActa neuropathologica communications2025
Development of CAR-T cell therapy for NF1/SWN-related nerve sheath tumor treatment.
Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Sensory innervation shapes cancer immunotherapy efficacy and adverse events.Journal for immunotherapy of cancer · 2026Review
- Review
- Benign tumors broaden the field of application for immunotherapy.Frontiers in immunology · 2025Review
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Authors and funding
8 authors.
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Abstract
Neurofibromatosis type 1 (NF1) and schwannomatosis (SWN) are rare genetic disorders with distinct genetic etiologies. Both syndromes are predominantly characterized by the development of multiple benign nerve sheath tumors, which typically arise from cranial/peripheral nerves. The management of NF1/SWN-associated benign nerve sheath tumors pose a substantial clinical challenge. In recent years, immunotherapy has demonstrated significant efficacy in treating various tumors, but its application to NF1/SWN has not been explored. In this study, we first evaluated the feasibility of chimeric antigen receptor (CAR)-T cell therapy for the treatment of benign NF1/SWN-related nerve sheath tumor by analyzing the expression of multiple antigens in 85 tumor samples. Our findings revealed that epidermal growth factor receptor (EGFR/HER1) was highly expressed in most samples, indicating its potential as an ideal target for CAR-T cell therapy. Additionally, TGFβ1 and PDL1, key inhibitory regulators of T cell function within solid tumor microenvironment (TME), were universally overexpressed in these samples, highlighting the immunosuppressive nature of NF1/SWN tumors. To target HER1, we constructed CARs using three distinct scFvs (806, E2 and NEC). All three types of CAR-T cells demonstrated significant tumor-eliminating capability against NF1/SWN tumor cell lines, with 806 CAR-T cells showing the highest efficacy. Considering the immunosuppressive TME, we knocked out TGFBR2 and/or PDCD1 in 806 CAR-T cells using CRISPR/Cas9. Their anti-tumor efficacy was further evaluated using a 3D tumor spheroid model, and the gene-edited 806 CAR-T cells exhibited superior anti-tumor efficacy. In conclusion, we identified HER1 as a target for CAR-T cell therapy in NF1/SWN-related nerve sheath tumors, and developed anti-HER1 CAR-T cells that effectively eliminated NF1/SWN tumor cells, providing a promising therapeutic strategy for patients with these conditions.
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