title: A bispecific antibody directly induces lymphoma cell death by simultaneously targeting CD20 and HLA-DR.
abstract: OBJECTIVE
  Both CD20 and HLA-DR antigens are highly expressed on a variety of B-cell lymphomas and are therapeutic targets in antibody-based lymphoma therapy. The aim of this study was to evaluate the anti-tumor effect of a bispecific antibody CD20-HLA-DR DVD-Ig on B-cell lymphoma.
  
  
  METHODS
  The gene for bispecific antibody CD20-HLA-DR DVD-Ig was constructed and expressed in FreeStyle™293-F cells, followed by purification. Their functions were characterized for binding to CD20 and HLA-DR and for cytotoxicity against B-cell lymphoma.
  
  
  RESULTS
  The bispecific antibody CD20-HLA-DR DVD-Ig was engineered using the DNA fragments for the anti-CD20 rituximab and anti-HLA-DR hL243γ1. The CD20-HLA-DR DVD-Ig bound simultaneously to both CD20 and HLA-DR, induced potent complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against B-cell lymphoma, and elicited homotypic adhesion and actin reorganization. Treatment of a mixture of human whole blood and Raji cells with CD20-HLA-DR DVD-Ig effectively depleted Raji cells and had a little toxicity against normal B cells.
  
  
  CONCLUSIONS
  Our data indicated that targeting both CD20 and HLA-DR was an effective way against NHL, suggesting that CD20-HLA-DR DVD-Ig may be a promising therapeutic agent for B-cell lymphoma.
authors.affiliation: Endocrinology Department, Affiliated Hospital of the Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, People's Republic of China. zjing1125@163.com.|Cancer Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People's Republic of China. zjing1125@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Endocrinology Department, Affiliated Hospital of the Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.affiliation: Endocrinology Department, Affiliated Hospital of the Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, People's Republic of China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Endocrinology Department, Affiliated Hospital of the Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, People's Republic of China. fangyi307@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
mesh_terms: D018033:Antibodies, Bispecific / Q000235:genetics* / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015202:Protein Engineering; D000069283:Rituximab / Q000235:genetics / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; D018951:Antigens, CD20; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D000069283:Rituximab
keywords: Bispecific antibody; CD20; Cell death; HLA-DR; Lymphoma