Article
Identification of new antigens in NF2-associated vestibular schwannoma and malignant peripheral nerv sheath tumours for CAR-T cell therapy
Identifizierung neuer Antigene bei NF2-assoziierten Vestibularisschwannomen und Malignen Peripheren Nervenscheidentumoren für CAR-T-Zell-Therapie
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Authors
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Felix Kugler
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Neurochirurgie, Würzburg, Deutschland
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Camelia-Maria Monoranu
- Universitätsklinikum Würzburg, Pathologie, Würzburg, Deutschland
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Cordula Matthies
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Neurochirurgie, Würzburg, Deutschland
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Ralf-Ingo Ernestus
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Neurochirurgie, Würzburg, Deutschland
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Mario Löhr
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Neurochirurgie, Würzburg, Deutschland
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Carsten Hagemann
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Neurochirurgie, Würzburg, Deutschland
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Vera Dufner
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Neurochirurgie, Würzburg, Deutschland
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Maria Breun
- Universitätsklinikum Würzburg, Klinik und Poliklinik für Neurochirurgie, Würzburg, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: CAR-T cells have emerged as a promising tool for immunotherapy in oncological patients. Previous studies could show evidence for various solid tumor entities like e.g. glioblastoma. Since nerve sheath tumors like NF2-associated Vestibular Schwannoma (NF2-VS) as well as Malignant Peripheral Nerve Sheath Tumors (MPNST) cause severe morbidity and mortality, more systemic and individual treatment strategies are required. In order to identify new targets, we examined the expression of seven different antigens in NF2-VS and MPNST in view of CAR-T cell therapies.
Methods: Tissue samples of twelve patients with NF2-VS and four patients with MPNST were analyzed for expression of B7H3, CSPG4, GD2, IL13Rα2, NY-ESO-1, Podoplanine (PDPN) and ROR2 by immunohistochemistry. In NF2-VS tissue, Antoni A and Antoni B areas were distinguished and evaluated separately. Healthy sural nerve tissue of two specimens served as control. Five representative areas of each slide were evaluated for the calculation of the H-score to compare antigen expression between different tissues for each antigen.
Results: All 16 examined tumor tissues showed rather low expression of GD2 and IL13Rα2. Similarly, NY-ESO-1 overall was slightly expressed except for MPNST (median: 55.53). CSPG4 displayed highest expression in MPNST (median: 123.19). Compared to healthy nerve tissue, B7H3 was strongly expressed in MPNST (median: 192.32) as well as in Antoni A (median: 166.24) and Antoni B regions of NF2-VS (median: 201.74, p = 0.028, effect size r = 1.00). PDPN had high expression in Antoni A (median 156.68) areas, whilst Antoni B regions (median: 59.04) and MPNST (median: 70.13) displayed lower expression. Interestingly, ROR2 expression was significantly higher in Antoni A (median: 241.80) compared to Antoni B areas (median: 139.13, p = 0.021, effect size r = 0.69). Except for ROR2 (median: 155.66), all antigens revealed low expression in healthy sural nerve.
Conclusion: Our data suggest that B7H3 might be a promising CAR-T cell target in both MPNST and NF2-VS, whereas PDPN might serve as such in NF2-VS. Furthermore, despite of a considerable expression in healthy nerve tissue and significant expression differences between Antoni A and Antoni B areas, ROR2 might represent a potential antigen for CAR-T cells in nerve sheath tumors.
