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Although several MC- and SM-expressed cell surface antigens have been identified, no immune therapy has been developed for advSM so far. The receptor tyrosine kinase KIT (CD117) is highly expressed on MCs, exceeding the levels of expression on hematopoietic stem and progenitor cells (HSPC). Therefore, targeting CD117 in advSM could be of therapeutic value. In this study, we assessed the therapeutic potential of anti-CD117 chimeric antigen receptor (CAR) T-cells to target neoplastic MCs in SM. In vitro, anti-CD117-CAR T-cells efficiently lysed several SM-related human MC cell lines, MCs differentiated from SM patient-derived induced pluripotent stem (iPS) cells, and neoplastic bone marrow cells obtained from SM patients. Furthermore, in immunocompromised mice engrafted with an advSM-like MC cell\u00a0line, repetitive applications of anti-CD117-CAR T-cells were able to inhibit MC expansion. These data may pave the way for the development of anti-CD117-CAR T-cell therapies in advSM.<\/jats:p>","DOI":"10.1038\/s41375-026-02968-5","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:05:50Z","timestamp":1778151950000},"page":"1482-1493","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CAR T-cells targeting CD117 effectively eliminate mast cells in preclinical models of advanced systemic mastocytosis"],"prefix":"10.1038","volume":"40","author":[{"given":"Anne","family":"Kaiser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6886-5444","authenticated-orcid":false,"given":"Veronika","family":"Lysenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renier","family":"Myburgh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Volta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-9988","authenticated-orcid":false,"given":"Christian","family":"Pellegrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-8692","authenticated-orcid":false,"given":"Alexandre P. 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Research grants from Blueprint Medicines, 2. Honoraria: AB Science, Blueprint Medicines and Thermo Fisher. JB: Licence fee by Millipore\/Sigma for HMC-1. PV: 1. Research grant: AOP Orphan, 2. advisory board and consultancy honoraria: Novartis, Blueprint Medicines, Amgen, Cogent, Delbert, PentaBase, Daiichi Sankyo, Pfizer, AOP Orphan, Stemline. AK, VL, RM, LV, CP, APAT, DC, JP, MMB, MAST, MZ, THB, MGM declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}