{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:29:36Z","timestamp":1764786576103,"version":"3.46.0"},"reference-count":50,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"unspecified","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Grand-Ouest Groupama Foundation","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":[[2025,11,3]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Blinatumomab, inotuzumab or autologous anti-CD19 chimeric antigen receptor (CAR)-T cells have revolutionized the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, tumor escape through antigenic modulation accounts for almost 40% of subsequent relapses. Multi-antigen targeting strategies should be developed, and it is urgent to identify new targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the extensive immunophenotyping of 13 BCP-ALL from pediatric patients by using the BioLegend Human Cell Surface Marker Screening Kit. Then, to assess whether targeting each antigen with monoclonal antibodies could lead to leukemic cell lysis, long-term antibody-dependent cellular cytotoxicity (ADCC) assays were performed using murine monoclonal antibodies and human T cells armed with murine CD16.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>13 highly expressed antigens were selected. With the antibodies tested here, the most significant lysis was observed by targeting CD24 and CD156c. The double targeting of CD24-CD123 appeared to be even more effective. Triple targeting was associated with a reduction in ADCC activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CD24 therefore emerged as an effective target in BCP-ALL, and the combination of CD24 and CD123 as a potential effective double-targeting strategy. The combination of different recognition modalities (eg, a CAR and CD16) should be tested to determine whether it provides synergistic cytotoxic activity in triple targeting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012552","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:25:45Z","timestamp":1764786345000},"page":"e012552","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of multi-antigen targeting ADCC strategies in pediatric BCP-ALL"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1547-8229","authenticated-orcid":false,"given":"Audrey","family":"Grain","sequence":"first","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"},{"name":"Nantes Universit\u00e9, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2723-1103","authenticated-orcid":false,"given":"Jocelyn","family":"Ollier","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5148-3792","authenticated-orcid":false,"given":"Baptiste","family":"Le Calvez","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"},{"name":"Nantes Universit\u00e9, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie","family":"Guiet","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Thomas","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Laure","family":"Couec","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaux","family":"Camuset","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanny","family":"Rialland","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Eveillard","sequence":"additional","affiliation":[{"name":"Hematology Biology, University Hospital Centre Nantes, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Scotet","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5305-4502","authenticated-orcid":false,"given":"B\u00e9atrice","family":"Cl\u00e9menceau","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"2025120310254093000_13.12.e012552.1","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1038\/s41375-018-0094-0","article-title":"Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia & lymphoma study","volume":"32","author":"Sun","year":"2018","journal-title":"Leukemia"},{"key":"2025120310254093000_13.12.e012552.2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-580068"},{"key":"2025120310254093000_13.12.e012552.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00642"},{"key":"2025120310254093000_13.12.e012552.4","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3863"},{"key":"2025120310254093000_13.12.e012552.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01497-1"},{"key":"2025120310254093000_13.12.e012552.6","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-019-0705-x","article-title":"Clinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemia","volume":"12","author":"Zhao","year":"2019","journal-title":"J Hematol Oncol"},{"key":"2025120310254093000_13.12.e012552.7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1449"},{"key":"2025120310254093000_13.12.e012552.8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3775"},{"key":"2025120310254093000_13.12.e012552.9","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2021.2003532","article-title":"Novel adapter CAR-T cell technology for precisely controllable multiplex cancer targeting","volume":"10","author":"Seitz","year":"2021","journal-title":"Oncoimmunology"},{"key":"2025120310254093000_13.12.e012552.10","doi-asserted-by":"crossref","DOI":"10.1038\/bcj.2016.61","article-title":"Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts","volume":"6","author":"Cartellieri","year":"2016","journal-title":"Blood Cancer J"},{"key":"2025120310254093000_13.12.e012552.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1524155113"},{"key":"2025120310254093000_13.12.e012552.12","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1365"},{"key":"2025120310254093000_13.12.e012552.13","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-13-0099-T"},{"key":"2025120310254093000_13.12.e012552.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.10.014"},{"key":"2025120310254093000_13.12.e012552.15","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2019.00176","article-title":"The Emergence of Universal Immune Receptor T Cell Therapy for Cancer","volume":"9","author":"Minutolo","year":"2019","journal-title":"Front Oncol"},{"key":"2025120310254093000_13.12.e012552.16","doi-asserted-by":"crossref","first-page":"587","DOI":"10.4161\/mabs.25077","article-title":"The human natural killer cytotoxic cell line NK-92, once armed with a murine CD16 receptor, represents a convenient cellular tool for the screening of mouse mAbs according to their ADCC potential","volume":"5","author":"Cl\u00e9menceau","year":"2013","journal-title":"MAbs"},{"key":"2025120310254093000_13.12.e012552.17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.8.4196"},{"key":"2025120310254093000_13.12.e012552.18","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007423"},{"key":"2025120310254093000_13.12.e012552.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01281-7"},{"key":"2025120310254093000_13.12.e012552.20","doi-asserted-by":"crossref","DOI":"10.1186\/s12964-020-00617-7","article-title":"The Role of Immunological Synapse in Predicting the Efficacy of Chimeric Antigen Receptor (CAR) Immunotherapy","volume":"18","author":"Liu","year":"2020","journal-title":"Cell Commun Signal"},{"key":"2025120310254093000_13.12.e012552.21","doi-asserted-by":"crossref","first-page":"E352","DOI":"10.1002\/ajh.25235","article-title":"Heterogeneity of surface CD19 and CD22 expression in B lymphoblastic leukemia","volume":"93","author":"Rosenthal","year":"2018","journal-title":"Am J Hematol"},{"key":"2025120310254093000_13.12.e012552.22","doi-asserted-by":"crossref","DOI":"10.1126\/science.aan2507","article-title":"A pathology atlas of the human cancer transcriptome","volume":"357","author":"Uhlen","year":"2017","journal-title":"Science"},{"key":"2025120310254093000_13.12.e012552.23","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402504"},{"key":"2025120310254093000_13.12.e012552.24","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.120"},{"key":"2025120310254093000_13.12.e012552.25","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/cyto.b.22153","article-title":"Immunophenotypic portrait of leukemia-associated-phenotype markers in B acute lymphoblastic leukemia","volume":"106","author":"Boris","year":"2024","journal-title":"Cytometry B Clin Cytom"},{"key":"2025120310254093000_13.12.e012552.26","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/bjc.1998.518","article-title":"The Impact of Antigen Density and Antibody Affinity on Antibody-Dependent Cellular Cytotoxicity: Relevance for Immunotherapy of Carcinomas","volume":"78","author":"Velders","year":"1998","journal-title":"C Br J Cancer"},{"key":"2025120310254093000_13.12.e012552.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601473"},{"key":"2025120310254093000_13.12.e012552.28","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02194-14"},{"key":"2025120310254093000_13.12.e012552.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508123103"},{"key":"2025120310254093000_13.12.e012552.30","doi-asserted-by":"crossref","DOI":"10.3390\/jpm12081235","article-title":"CD24: A Novel Target for Cancer Immunotherapy","volume":"12","author":"Panagiotou","year":"2022","journal-title":"J Pers Med"},{"key":"2025120310254093000_13.12.e012552.31","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33249"},{"key":"2025120310254093000_13.12.e012552.32","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJM199105233242102","article-title":"Anti-B-cell monoclonal antibodies in the treatment of severe B-cell lymphoproliferative syndrome following bone marrow and organ transplantation","volume":"324","author":"Fischer","year":"1991","journal-title":"N Engl J Med"},{"key":"2025120310254093000_13.12.e012552.33","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1182\/blood.V92.9.3137","article-title":"Anti-B-cell monoclonal antibody treatment of severe posttransplant B-lymphoproliferative disorder: prognostic factors and long-term outcome","volume":"92","author":"Benkerrou","year":"1998","journal-title":"Blood"},{"key":"2025120310254093000_13.12.e012552.34","doi-asserted-by":"crossref","DOI":"10.1186\/1559-0275-8-9","article-title":"The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer?","volume":"8","author":"Duffy","year":"2011","journal-title":"Clin Proteomics"},{"key":"2025120310254093000_13.12.e012552.35","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6768"},{"key":"2025120310254093000_13.12.e012552.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2010.11.005"},{"key":"2025120310254093000_13.12.e012552.37","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2015.1123367","article-title":"ADAM10 new selective inhibitors reduce NKG2D ligand release sensitizing Hodgkin lymphoma cells to NKG2D-mediated killing","volume":"5","author":"Zocchi","year":"2016","journal-title":"Oncoimmunology"},{"key":"2025120310254093000_13.12.e012552.38","doi-asserted-by":"crossref","DOI":"10.1002\/jmv.28106","article-title":"Broadly neutralizing antibodies recognizing different antigenic epitopes act synergistically against the influenza B virus","volume":"95","author":"Zhai","year":"2023","journal-title":"J Med Virol"},{"key":"2025120310254093000_13.12.e012552.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.12.711"},{"key":"2025120310254093000_13.12.e012552.40","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2017.1421889","article-title":"Specific ADAM10 inhibitors localize in exosome-like vesicles released by Hodgkin lymphoma and stromal cells and prevent sheddase activity carried to bystander cells","volume":"7","author":"Tosetti","year":"2018","journal-title":"Oncoimmunology"},{"key":"2025120310254093000_13.12.e012552.41","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0739"},{"key":"2025120310254093000_13.12.e012552.42","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14133171","article-title":"Preferential Antibody and Drug Conjugate Targeting of the ADAM10 Metalloprotease in Tumours","volume":"14","author":"Yan","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2025120310254093000_13.12.e012552.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114494"},{"key":"2025120310254093000_13.12.e012552.44","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.207266"},{"key":"2025120310254093000_13.12.e012552.45","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-3312"},{"key":"2025120310254093000_13.12.e012552.46","first-page":"1720","article-title":"Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved antigrowth activity of a human breast cancer cell line in vitro and in vivo","volume":"8","author":"Spiridon","year":"2002","journal-title":"Clin Cancer Res"},{"key":"2025120310254093000_13.12.e012552.47","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines10102420","article-title":"Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas","volume":"10","author":"Atar","year":"2022","journal-title":"Biomedicines"},{"key":"2025120310254093000_13.12.e012552.48","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaw9414","article-title":"CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies","volume":"11","author":"Qin","year":"2019","journal-title":"Sci Transl Med"},{"key":"2025120310254093000_13.12.e012552.49","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1093750","article-title":"Preclinical evaluation of CD70-specific CAR T cells targeting acute myeloid leukemia","volume":"14","author":"Wu","year":"2023","journal-title":"Front Immunol"},{"key":"2025120310254093000_13.12.e012552.50","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1111\/jcmm.17810","article-title":"Design and preclinical testing of an anti-CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia","volume":"27","author":"Tigu","year":"2023","journal-title":"J Cell Mol Med"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-012552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:25:48Z","timestamp":1764786348000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-012552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,3]]},"published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1136\/jitc-2025-012552"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-012552","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]}}}