title: A novel antibody-drug conjugate anti-CD19(Fab)-LDM in the treatment of B-cell non-Hodgkin lymphoma xenografts with enhanced anticancer activity.
abstract: BACKGROUND
  Rituximab is widely used in clinical setting for the treatment of B malignant lymphoma and has achieved remarkable success. However, in most patients, the disease ultimately relapses and become resistant to rituximab. To overcome the limitation, there is still a need to find novel strategy for improving therapeutic efficacy.
  
  
  OBJECTIVE
  To construct genetically engineered antibody anti-CD19(Fab)-LDM, and verify the anticancer activity targeted toward B-lymphoma.
  
  
  METHODS
  The anticancer activity of anti-CD19(Fab)-LDM in vitro and in vivo was examined. In vitro, the binding activity and internalization of anti-CD19(Fab)-LDP were measured. Using comet assay and apoptosis, the cytotoxicity of energized fusion proteins was observed. From in vivo experiments, targeting of therapeutic effect and anticancer efficacy bythe fusion protein was verified.
  
  
  RESULTS
  Data showed that anti-CD19(Fab)-LDM does not only binding the cell surface but is also internalized into the cell. The energized fusion proteins anti-CD19(Fab)-LDM can induce DNA damage. Furthermore, significant in vivo therapeutic efficacy was observed.
  
  
  CONCLUSIONS
  The present study demonstrated that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced cytotoxicity compared to LDM alone. One of the most powerful advantages of anti-CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted therapy for B-cell lymphoma.
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Linlin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Bao
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Fan
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , China and.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xiong
authors.affiliation: b Department of Oncology , Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College , China.
authors.forename: Yongsu
authors.initials: Y
authors.lastname: Zhen
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000276:immunology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D053281:Enediynes / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D064593:Heterografts; D006801:Humans; D016393:Lymphoma, B-Cell / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D004337:Drug Carriers; D053281:Enediynes; D011993:Recombinant Fusion Proteins; C058024:C 1027
keywords: Anti-CD19(Fab)-LDM; B-lymphoma; DNA damage; internalization; targeted therapy