{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:25:18Z","timestamp":1793899518706,"version":"4.8.0"},"reference-count":52,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,23]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Organ transplantation is a pivotal treatment for patients with organ failure. ABO-incompatible (ABOi) transplantation, developed to expand the donor pool, presents significant clinical challenges due to preexisting antibodies targeting ABO antigens on donor organs. Current therapies using broad B-cell depletion, such as rituximab, effectively reduce antibody-mediated rejection but increase infection risks. Therefore, there is a critical need for targeted methods to specifically eliminate ABO-responsive B cells. Here, we developed a novel bispecific antibody-ligand conjugate (BiALC) platform designed to selectively target ABO-responsive B cells. Using synthetic trisaccharide A antigens conjugated to T-cell\u2013recruiting Fab fragments, our optimized hexameric construct, (A3-peg)2-\u03b1CD3, demonstrated enhanced affinity and potent cytotoxicity specifically against type A antigen\u2013responsive B cells. Notably, BiALC maintained robust efficacy even in the presence of circulating anti-A antibodies. In murine models, (A3-peg)2-\u03b1CD3 selectively depleted A-responsive B cells without broadly affecting total immunoglobulin M\u2013positive (IgM+) and IgG+ B-cell populations, preserving overall immune competence. Similarly, the human-compatible BiALC, (A3-peg)2-\u03b1hCD3, effectively and selectively depleted type A\u2013responsive B cells from human peripheral blood mononuclear cells, with potency comparable with that of rituximab, while sparing total antibody-secreting cells. Overall, the BiALC strategy offers a promising antigen-specific approach to reduce rejection risks in ABOi transplantation without inducing broad immunosuppression through nonspecific pan\u2013B-cell depletion, supporting its potential for clinical translation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030660","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T21:28:53Z","timestamp":1767821333000},"page":"1928-1940","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["Selective depletion of ABO-responsive B cells by T-cell\u2013engaging bispecific antibody conjugates for ABOi transplantation"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-6295","authenticated-orcid":false,"given":"Hyeong Ryeol","family":"Choi","sequence":"first","affiliation":[{"name":"1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea"},{"name":"2Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4829-6157","authenticated-orcid":false,"given":"Honglin","family":"Piao","sequence":"additional","affiliation":[{"name":"3Department of Medicine, Graduate School, Seoul National University College of Medicine, Seoul, Republic of Korea"},{"name":"4Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea"},{"name":"5Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-3741","authenticated-orcid":false,"given":"Shafrizal Rasyid","family":"Atriardi","sequence":"additional","affiliation":[{"name":"6Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9125-0528","authenticated-orcid":false,"given":"In","family":"Kang","sequence":"additional","affiliation":[{"name":"7Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taekyung","family":"Chang","sequence":"additional","affiliation":[{"name":"1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1748-8798","authenticated-orcid":false,"given":"Serin","family":"Kim","sequence":"additional","affiliation":[{"name":"8College of Pharmacy, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-1161","authenticated-orcid":false,"given":"Joon Young","family":"Jang","sequence":"additional","affiliation":[{"name":"4Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-3334","authenticated-orcid":false,"given":"Gwang-Min","family":"Lee","sequence":"additional","affiliation":[{"name":"3Department of Medicine, Graduate School, Seoul National University College of Medicine, Seoul, Republic of Korea"},{"name":"4Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7741-7184","authenticated-orcid":false,"given":"Kyeong Cheon","family":"Jung","sequence":"additional","affiliation":[{"name":"9Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanifah","family":"Mardhiyah","sequence":"additional","affiliation":[{"name":"6Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-8937","authenticated-orcid":false,"given":"Fazsa Islamianti","family":"Machmud","sequence":"additional","affiliation":[{"name":"6Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Park","sequence":"additional","affiliation":[{"name":"10Department of Chemistry, University of Ulsan, Ulsan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-037X","authenticated-orcid":false,"given":"Sang Kook","family":"Woo","sequence":"additional","affiliation":[{"name":"6Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5378-7797","authenticated-orcid":false,"given":"Jaeseok","family":"Yang","sequence":"additional","affiliation":[{"name":"4Division of Nephrology, 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