{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:14:53Z","timestamp":1780600493874,"version":"3.54.1"},"reference-count":45,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"unspecified","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cellectis S.A.","award":["N.A."],"award-info":[{"award-number":["N.A."]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,7,7]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Autologous BCMA-specific CAR T-cell therapies have substantial activity in multiple myeloma (MM). However, due to logistical limitations and BCMA<jats:sup>low<\/jats:sup> relapses, there is a need for alternatives. UCARTCS1 cells are \u2018off-the-shelf\u2019 allogeneic CAR T-cells derived from healthy donors targeting SLAMF7 (CS1), which is highly expressed in MM cells. In this study, we evaluated the preclinical activity of UCARTCS1 in MM cell lines, in bone marrow (BM) samples obtained from MM patients and in an MM mouse model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Luciferase-transduced MM cell lines were incubated with UCARTCS1 cells or control (non-transduced, SLAMF7\/TCR\u03b1\u03b2 double knock-out) T-cells at different effector to target ratios for 24 hours. MM cell lysis was assessed by bioluminescence. Anti-MM activity of UCARTCS1 was also evaluated in 29 BM samples obtained from newly diagnosed patients (n=10), daratumumab-na\u00efve relapsed\/refractory patients (n=10) and daratumumab-refractory patients (n=9) in 24-hour flow cytometry-based cytotoxicity assays. Finally, UCARTCS1 activity was assessed in mouse xenograft models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>UCARTCS1 cells induced potent CAR-mediated, and dose-dependent lysis of both MM cell lines and primary MM cells. There was no difference in ex vivo activity of UCARTCS1 between heavily pretreated and newly diagnosed patients. In addition, efficacy of UCARTCS1 was not affected by SLAMF7 expression level on MM cells, proportion of tumor cells, or frequency of regulatory T-cells in BM samples obtained from MM patients. UCARTCS1 treatment eliminated SLAMF7<jats:sup>+<\/jats:sup> non-malignant immune cells in a dose-dependent manner, however lysis of normal cells was less pronounced compared to that of MM cells. Additionally, durable anti-MM responses were observed with UCARTCS1 in an MM xenograft model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results demonstrate that UCARTCS1 has potent anti-MM activity against MM cell lines and primary MM cells, as well as in an MM xenograft model and support the evaluation of UCARTCS1 in patients with advanced MM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-008769","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T01:41:39Z","timestamp":1721958099000},"page":"e008769","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Preclinical activity of allogeneic SLAMF7-specific CAR T-cells (UCARTCS1) in multiple myeloma"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04142619","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0191-4343","authenticated-orcid":false,"given":"Charlotte L B M","family":"Korst","sequence":"first","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassilis S C","family":"Bruins","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meliha","family":"Cosovic","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inoka","family":"Twickler","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie P M","family":"Verkleij","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Le Clerre","sequence":"additional","affiliation":[{"name":"Cellectis SA, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-7786","authenticated-orcid":false,"given":"Maria","family":"Themeli","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Chion-Sotinel","sequence":"additional","affiliation":[{"name":"Cellectis SA, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Galetto","sequence":"additional","affiliation":[{"name":"Cellectis SA, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuna","family":"Mutis","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels W C J","family":"van de Donk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center, Amsterdam, The 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