{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:20:22Z","timestamp":1790626822548,"version":"4.1.0"},"reference-count":18,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,30]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>CD47 is overexpressed on the surface of many types of cancer cells, including T-cell acute lymphoblastic leukemia (T-ALL) cells. In this study, we have developed a diphtheria toxin (DT)\u2013based bivalent anti-human CD47 immunotoxin (bi-CD47-IT) for the targeted therapy of CD47+ cancers using a unique DT-resistant yeast Pichia pastoris expression system. Bi-CD47-IT demonstrated compelling in\u00a0vivo efficacy in multiple T-ALL cell line\u2013derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Bi-CD47-IT significantly prolonged the median survival of the tumor-bearing mice and highly effectively depleted the T-ALL blast cells in the peripheral blood, spleen, liver, bone marrow, brain, and spinal cord in the T-ALL CDX and PDX mouse models. Bi-CD47-IT cured 60% of tumor-bearing mice in a T-ALL Molt-4 CDX mouse model. Because CD47 is also expressed on normal tissues, including red blood cells and lymphocytes, specificity is a concern. We thus analyzed the in\u00a0vitro binding avidity and hemagglutination of bi-CD47-IT in human red blood cells, finding no binding or hemagglutination. We further performed a toxicity study of bi-CD47-IT in humanized mice, which showed that bi-CD47-IT transiently depleted the human lymphocytes for \u223c4 weeks after the 10-day treatment. No clinical adverse events were observed. As a result, bi-CD47-IT appears to possess the \u201coptimal\u201d binding avidity, with effective binding to human CD47+ T-ALL tumor cells, no binding to human red blood cells, and weak binding to human lymphocytes. We believe that bi-CD47-IT is a promising and safe therapeutic drug candidate for the targeted therapy of CD47+ cancers.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024025277","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T20:28:50Z","timestamp":1732048130000},"page":"508-519","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":8,"title":["Bivalent CD47 immunotoxin for targeted therapy of T-cell acute lymphoblastic leukemia"],"prefix":"10.1182","volume":"145","author":[{"given":"Jihong","family":"Ma","sequence":"first","affiliation":[{"name":"1Division of Plastic & Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"},{"name":"2Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-3867","authenticated-orcid":false,"given":"Zhaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"1Division of Plastic & Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"},{"name":"2Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Mintzlaff","sequence":"additional","affiliation":[{"name":"1Division of Plastic & Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"},{"name":"2Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Division of Plastic & Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"},{"name":"2Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Ramakrishna","sequence":"additional","affiliation":[{"name":"1Division of Plastic & Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"},{"name":"2Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Davila","sequence":"additional","affiliation":[{"name":"3Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-4288","authenticated-orcid":false,"given":"Matthew T.","family":"Witkowski","sequence":"additional","affiliation":[{"name":"4Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-7378","authenticated-orcid":false,"given":"M. Scott","family":"Lucia","sequence":"additional","affiliation":[{"name":"5Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"6Department of Medicine, University of Colorado Hospital, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Pomfret","sequence":"additional","affiliation":[{"name":"2Division of Transplant Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Mathes","sequence":"additional","affiliation":[{"name":"1Division of Plastic & Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz 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