{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T04:26:10Z","timestamp":1793939170897,"version":"4.8.0"},"reference-count":43,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"714","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,9,20]]},"abstract":"<jats:p>In the absence of cell surface cancer-specific antigens, immunotherapies such as chimeric antigen receptor (CAR) T cells, monoclonal antibodies, or bispecific T cell engagers typically target lineage antigens. Currently, such immunotherapies are individually designed and tested for each disease. This approach is inefficient and limited to a few lineage antigens for which the on-target\/off-tumor toxicities are clinically tolerated. Here, we sought to develop a universal CAR T cell therapy for blood cancers directed against the pan-leukocyte marker CD45. To protect healthy hematopoietic cells, including CAR T cells, from CD45-directed on-target\/off-tumor toxicity while preserving the essential functions of CD45, we mapped the epitope on CD45 that is targeted by the CAR and used CRISPR adenine base editing to install a function-preserving mutation sufficient to evade CAR T cell recognition. Epitope-edited CD45 CAR T cells were fratricide resistant and effective against patient-derived acute myeloid leukemia, B cell lymphoma, and acute T cell leukemia. Epitope-edited hematopoietic stem cells (HSCs) were protected from CAR T cells and, unlike CD45 knockout cells, could engraft, persist, and differentiate in vivo. Ex vivo epitope editing in HSCs and T cells enables the safe and effective use of CD45-directed CAR T cells and bispecific T cell engagers for the universal treatment of hematologic malignancies and might be exploited for other diseases requiring intensive hematopoietic ablation.<\/jats:p>","DOI":"10.1126\/scitranslmed.adi1145","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T13:58:11Z","timestamp":1693490291000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":132,"title":["Epitope base editing CD45 in hematopoietic cells enables universal blood cancer immune therapy"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-7582","authenticated-orcid":true,"given":"Nils","family":"Wellhausen","sequence":"first","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3808-4281","authenticated-orcid":true,"given":"Ryan P.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-7666","authenticated-orcid":true,"given":"Stefanie","family":"Lesch","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-5686","authenticated-orcid":true,"given":"Nils W.","family":"Engel","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0059-5677","authenticated-orcid":true,"given":"Austin K.","family":"Rennels","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-946X","authenticated-orcid":true,"given":"Donna","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2167-750X","authenticated-orcid":true,"given":"Friederike","family":"Herbst","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-9449","authenticated-orcid":true,"given":"Regina M.","family":"Young","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9273-0278","authenticated-orcid":true,"given":"K. Christopher","family":"Garcia","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA."},{"name":"Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-8512","authenticated-orcid":true,"given":"David","family":"Weiner","sequence":"additional","affiliation":[{"name":"Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0241-3557","authenticated-orcid":true,"given":"Carl H.","family":"June","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Parker Institute for Cancer Immunotherapy at University of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7946-7778","authenticated-orcid":true,"given":"Saar I.","family":"Gill","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-813493"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609783"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509277"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011994"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(20)30277-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01969-y"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015526"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.140946"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.013"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1819992116"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0277-8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/73208"},{"key":"e_1_3_2_15_2","first-page":"89","article-title":"Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model","volume":"52","author":"van der Jagt R. 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