title: Diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19+tumors.
abstract: CD19 is expressed on normal and neoplastic B cells and is a promising target for immunotherapy. However, there is still an unmet need to further develop novel therapeutic drugs for the treatment of the refractory/relapsing human CD19+tumors. We have developed a diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19+tumors. We have constructed three isoforms of the CD19 immunotoxin: monovalent, bivalent, and foldback diabody. In vitro binding affinity and efficacy analysis demonstrated that the bivalent isoform had the highest binding affinity and in vitro efficacy. The in vivo efficacy of the CD19 immunotoxins was assessed using human CD19+JeKo-1 tumor-bearing NOD/SCID IL-2 receptor γ-/-(NSG) mouse model. In these animals, CD19 immunotoxins significantly prolonged the median survival from 31 days in controls to 34, 36, and 40 days in animals receiving the monovalent isoform, foldback diabody isoform, and bivalent isoform, respectively. The bivalent CD19 immunotoxin is a promising therapeutic drug candidate for targeting relapsing/refractory human CD19+tumors.
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|Division of Cardiac Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.|TBRC Laboratories, Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Christene A
authors.initials: CA
authors.lastname: Huang
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Zhirui
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics; D004167:Diphtheria Toxin / Q000235:genetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000628:therapy*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D018941:Antigens, CD19; C000604811:CD19 molecule, human; D004167:Diphtheria Toxin; D000922:Immunotoxins; D004247:DNA
keywords: 
  Pichia Pastoris
  ; CD19+ tumor; diphtheria toxin; human CD19; immunotoxin